HK1032392A - Sulfonamide compounds and medicinal use thereof - Google Patents

Description

Sulfonamide compound and pharmaceutical use thereof

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Technical Field

The present invention relates to a novel sulfonamide compound, and more particularly to a novel sulfonamide compound having a hypoglycemic activity or a PDE-V inhibitory action, and a salt thereof. The present invention also relates to a method for producing the above sulfonamide compound and a salt thereof. The present invention also relates to a pharmaceutical containing the above sulfonamide compound or a salt thereof as an active ingredient. Background

The present invention addresses the problem of providing a novel sulfonamide compound and a pharmaceutically acceptable salt thereof, and a pharmaceutical preparation containing the sulfonamide compound or the pharmaceutically acceptable salt thereof as an active ingredient, which can be used for the treatment or prevention of glucose tolerance disorder, diabetes (such as type II diabetes), diabetic complications (e.g., diabetic gangrene, diabetic arthropathy, diabetic bone resorption, diabetic glomerulosclerosis, diabetic nephropathy, diabetic skin disorder, diabetic neuropathy, diabetic cataract, diabetic retinopathy, etc.), insulin resistance syndrome (insulin receptor abnormality, Rabson-Mendenhall syndrome, leprechaunism syndrome, Kobberlig-nnigan syndrome, Seip syndrome, Lawrence syndrome, Cushing syndrome, acromegaly syndrome), polycystic ovary syndrome, hyperlipidemia, atherosclerosis, diabetes mellitus, diabetes, Cardiovascular diseases (angina pectoris, heart failure, etc.), hyperglycemia (for example, hyperglycemia characterized by abnormal sugar metabolism such as eating disorder), hypertension, pulmonary hypertension, blood stasis heart failure, glomerular diseases (for example, diabetic glomerulosclerosis, etc.), tubulointerstitial diseases (for example, kidney diseases induced by FK506, cyclosporin, etc.), renal failure, vascular stenosis (for example, vascular stenosis after percutaneous arterioplasty), peripheral vascular diseases, stroke, chronic reversible occlusive diseases (for example, bronchitis, asthma (chronic asthma, allergic asthma)), autoimmune diseases, allergic rhinitis, urticaria, glaucoma, diseases characterized by intestinal motility disorder (for example, allergic intestinal syndrome), impotence (for example, organic impotence, psychogenic impotence, etc.), nephritis, restenosis after carcinomatosis or PTCA, pancreatitis, or pancreatitis, And cachexia (for example, weight loss due to lipolysis, muscular degeneration, anemia, edema, and anorexia in chronic diseases such as cancer, tuberculosis, endocrine diseases, and AIDS). Description of the invention

The novel sulfonamide compound of the present invention is a sulfonamide compound represented by the general formula (I) [ hereinafter referred to as the objective compound (I) ].

R¹-SO₂NHCO-A-X-R²(I) (in the formula, R¹Represents an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, a cyclo-lower alkyl group which may be substituted, an aryl group which may be substituted or a heterocyclic group which may be substituted;

a represents a polycyclic heterocycle which may be substituted other than benzimidazolyl, indolyl, 4, 7-dihydrobenzimidazolyl and 2, 3-dihydrobenzoxazinyl;

x represents an alkylene group, an oxo group, an oxa lower alkylene group, a lower alkyleneoxo group, a carbonyl group, a lower alkenylene group, an imino group which may be substituted, an imino lower alkylene group which may be substituted, a lower alkyleneimino group which may be substituted, a thia lower alkylene group or a lower alkylenethia group;

R²represents an aryl group which may be substituted, a heterocyclic group which may be substituted or a substituted biphenyl group;

wherein, when A represents a 3H-imidazo [ 4, 5-b ] pyridyl group substituted with a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a biphenyl group substituted with a group other than tetrazolyl;

when A represents a quinolyl group substituted by a lower alkyl group, R ²Represents an optionally substituted aryl group; a heterocyclic group which may be substituted; or biphenyl substituted with at least 1 substituent selected from the group consisting of alkyl, cyclo-lower alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocyclic lower alkyl other than tetrazolylmethyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carbamoyl, mono-lower alkylcarbamoyl, di-lower alkylcarbamoyl, nitro, halo-lower alkyl, aryl-lower alkenyl, aryl-lower alkoxy, lower alkoxy substituted with substituted amino, cyclo-lower alkyl-lower alkoxy, cyclo-lower alkyl, aryloxy-lower alkyl, acyloxy-lower alkyl, hydroxy-lower alkyl, mono-or di-lower alkylLower alkylamino lower alkyl, aryl lower alkoxy lower alkyl, arylthio lower alkyl, heterocyclic lower alkoxy, heterocyclic oxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted).

Preferred salts of the object compound (I) are nontoxic pharmaceutically acceptable salts which are customary, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, salts of ammonium salts with inorganic bases, organic amine salts such as triethylamine, pyridine, picoline, ethanolamine and triethanolamine, inorganic acid salts such as hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid, organic acid salts such as formic acid, acetic acid, trifluoroacetic acid, maleic acid and tartaric acid, sulfonic acid addition salts such as methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid, and salts or acid addition salts with basic groups or acidic amino acids such as arginine, aspartic acid and glutamic acid.

Object (I) of the present invention and salts thereof can be prepared according to the process shown in the following reaction scheme. The preparation method comprises the following steps:

R¹-SO₂NH₂ (II) + HOOC-A-X-R² (III)

or a salt thereof or a reactive derivative of the carboxyl group thereof or a salt thereof

—————→ R¹-SO₂NHCO-A-X-R² (I)

Or a salt thereof

(wherein each symbol is the same as described above)

The object compound (I) of the present invention and a salt thereof can also be prepared according to the method shown in the following reaction scheme. The preparation method 2 comprises the following steps:(in the formula, R²⁰¹Is an aryl group which may be substituted, a heterocyclic group which may be substituted or a biphenyl group which may be substituted These groups have at least an alkynyl group, an aryl lower alkenyl group, a terminal nitro group or a terminal formyl group, R²⁰²Aryl which may be substituted, heterocyclic group which may be substituted or biphenyl which may be substituted, these groups having at least alkyl, aryl lower alkyl, terminal amino or hydroxymethyl, the others being the same as above) preparation method 3:(in the formula, R²⁰³Is an optionally substituted aryl group, an optionally substituted heterocyclic group or an optionally substituted biphenyl group having at least a terminal formyl group, R²⁰⁴Aryl which may be substituted, heterocyclic group which may be substituted, or biphenyl which may be substituted, these groups having at least carboxyl group, the other being the same as above) preparation method 4:

(in the formula, R²⁰⁵Is an optionally substituted aryl group, an optionally substituted heterocyclic group or an optionally substituted biphenyl group having at least a hydroxy lower alkyl group, R²⁰⁶Aryl which may be substituted, heterocyclic group which may be substituted or biphenyl which may be substituted, these groups having at least acyloxyloweralkyl group, the others being the same as above) preparation method 5:

(in the formula, R²⁰⁷Aryl which may be substituted, heterocyclic group which may be substituted or biphenyl which may be substituted, these groups having at least aryloxy lower alkyl, the other being the same as above) preparation method 6:

(in the formula, R²⁰⁸Aryl which may be substituted, heterocyclic group which may be substituted or biphenyl which may be substituted, these groups having at least protected carboxyl group, the other being the same as above) preparation method 7:

(in the formula, R²⁰⁹Is optionally substituted arylA heterocyclic group which may be substituted or a biphenyl group which may be substituted, these groups having at least an amide group which may be substituted, the others being the same as above) preparation method 8:

(in the formula, R²¹⁰Is a substituted aryl group having at least a halogen atom,is a nitrogen-containing heterocyclic group, R²¹¹Substituted aryl, substituted by at least a nitrogen-containing heterocyclic group, the other symbols being as defined above)

Preferred examples of the above and below definitions in this specification are described in detail below.

The term "lower" means 1 to 6 carbon atoms unless otherwise specified.

The term "higher" means 7 to 20 carbon atoms unless otherwise specified.

The "alkyl" and "alkyl moiety" are preferably straight-chain or branched lower alkyl and higher alkyl. Preferred specific examples are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, isopentyl, sec-pentyl, tert-pentyl, methylbutyl, 1-dimethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3-ethylbutyl, 1-dimethylbutyl, 2-dimethylbutyl, 3-dimethylbutyl, 1-ethyl-1-methylpropyl, n-heptyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1-ethylpentyl, 2-ethylpentyl, 3-ethylpentyl, pentyl, 4-ethylpentyl group, 1-dimethylpentyl group, 2-dimethylpentyl group, 3-dimethylpentyl group, 4-dimethylpentyl group, 1-propylbutyl group, n-octyl group, 1-methylheptyl group, 2-methylheptyl group, 3-methylheptyl group, 4-methylheptyl group, 5-methylheptyl group, 6-methylheptyl group, 1-ethylhexyl group, 2-ethylhexyl group, 3-ethylhexyl group, 4-ethylhexyl group, 5-ethylhexyl group, 1-dimethylhexyl group, 2-dimethylhexyl group, 3-dimethylhexyl group, 4-dimethylhexyl group, 5-dimethylhexyl group, 1-propylpentyl group, etc.

Among them, an alkyl group having 2 to 8 carbon atoms is particularly preferable.

"alkenyl" and "lower alkenyl moiety" are preferably straight-chain or branched lower and higher alkenyl groups, such as vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1, 3-butadienyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl and the like.

Among them, alkenyl groups having 2 to 8 carbon atoms are particularly preferable.

The "alkynyl group" is preferably a straight-chain or branched lower or higher alkynyl group, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 2-methyl-3-butynyl, 1-dimethyl-2-butynyl, 1-hexynyl, 5-hexynyl and the like.

Among them, particularly preferred is an alkynyl group having 2 to 8 carbon atoms.

"Cyclolower alkyl" is cycloalkyl of 3 to 10 carbons, preferably 3 to 7 carbons, preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and the like, more preferably cyclopropyl, cyclobutyl, cyclohexyl.

Suitable examples of "aryl" are phenyl, naphthyl, and pentalenyl radicals and the like C₆～C₁₀Aryl, of which phenyl and naphthyl are preferred.

The "heterocyclic group" is a saturated or unsaturated, monocyclic or polycyclic heterocyclic group containing at least 1 hetero ring atom such as an oxygen atom, a sulfur atom, a nitrogen atom or a selenium atom, and among them, a polycyclic heterocyclic group (particularly, a bicyclic heterocyclic group) and an unsaturated 3-to 8-membered monocyclic heterocyclic group containing 1 to 2 sulfur atoms are preferable.

Preferred heterocyclic groups are, for example, the following.

First, the "monocyclic heterocyclic group" is exemplified by the following. For example:

unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic group having 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl (for example, 4H-1, 2, 4-triazolyl, 1H-1, 2, 3-triazolyl, 2H-1, 2, 3-triazolyl and the like), tetrazolyl (for example, 1H-tetrazolyl, 2H-tetrazolyl) and the like;

saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 4 nitrogen atoms, for example, pyrrolidinyl, imidazolinyl, piperidinyl, piperazinyl, etc.;

unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl (for example, 1, 2, 4-oxadiazolyl, 1, 3, 4-oxadiazolyl, 1, 2, 5-oxadiazolyl, etc.), etc.;

Saturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic group containing 1-2 oxygen atoms and 1-3 nitrogen atoms, such as morpholinyl, sdeonyl;

unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic group containing 1-2 sulfur atoms and 1-3 nitrogen atoms, for example, thiazolyl, isothiazolyl, thiadiazolyl (e.g., 1, 2, 3-thiadiazolyl, 1, 2, 4-thiadiazolyl, 1, 3, 4-thiadiazolyl, 1, 2, 5-thiadiazolyl, etc.), dihydrothiazinyl, etc.;

saturated 3-8-membered (more preferably 5-6-membered) heteromonocyclic group containing 1-2 sulfur atoms and 1-3 nitrogen atoms, such as thiazolidinyl;

unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atoms, such as thienyl, dihydrodithiinyl, dihydrodithiino;

unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atoms, such as tetrahydrofuranyl group, tetrahydropyranyl group and the like;

unsaturated 3-to 8-membered (more preferably 5-or 6-membered) heteromonocyclic group containing 1 oxygen atom, such as furyl group and the like;

spiroheterocyclic groups having 1 to 2 oxygen atoms such as dioxaspiro undecanyl (e.g., 1, 5-dioxaspiro [ 5, 5 ] undecanyl), etc.;

Unsaturated 3-to 8-membered (more preferably 5-to 6-membered) heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 2 sulfur atoms, for example, dihydrooxathinyl (dihydrooxathinyl) and the like.

The "polycyclic heterocyclic group" is exemplified by the following.

A saturated or unsaturated 7-to 12-membered (more preferably 8-to 10-membered) polycyclic (more preferably bicyclic) heterocyclic group containing 1 to 4 nitrogen atoms in addition to the benzimidazolyl group and the indolyl group.

Specific examples thereof include 2, 3-dihydrobenzimidazolyl, pyrazolopyrimidinyl (e.g., pyrazolo [ 1, 5-a ] pyrimidinyl, etc.), tetrahydropyrazolopyrimidinyl (e.g., 4, 5, 6, 7-tetrahydropyrazolo [ 1, 5-a ] pyrimidinyl, etc.), imidazopyrazolyl (e.g., 4H-imidazo [ 1, 2-b ] pyrazolyl, etc.), dihydroimidazopyrazolyl (e.g., 2, 3-dihydroimidazo [ 1, 2-b ] pyrazolyl, etc.), imidazopyridinyl (e.g., imidazo [ 1, 5-a ] (or [ 1, 2-a ]), or [ 3, 4-a ]) pyridyl, 1H (or 3H) -imidazo [ 4, 5-b ] (or [ 4, 5-c ]) pyridyl), pyrrolopyridyl (e.g., 1H-pyrrolo [ 3, 2-b ] pyridyl group, etc.), pyrazolopyridyl group (e.g., pyrazolo [ 1, 5-a ] (or [ 2, 3-a ]) pyridyl group, 1H (or 2H) -pyrazolo [ 4, 3-b ] pyridyl group, etc.), benzopyrazolyl group (e.g., 1H (or 2H) -benzo [ c ] pyrazolyl group, etc.), dihydrobenzimidazolyl group, benzotriazolyl group (e.g., benzo [ d ] -1H-1, 2, 3 ] triazolyl group, etc.), indolizinyl group, isoindolyl group (e.g., 1H-isoindolyl group, etc.), indazolyl group (e.g., 1H (or 2H, or 3H) -indazolyl group, etc.), indolinyl group, isoindolinyl group, purinyl group, quinolizinyl group (e.g., 4H-quinolyl group, etc.), isoquinolyl group, quinolyl group, phthalazinyl group, naphthylamino group (e.g., 1, 8-naphthylamino group, etc.), quinoxalinyl group, Dihydroquinoxalinyl (e.g., 1, 2-dihydroquinoxalinyl, etc.), tetrahydroquinoxalinyl (e.g., 1, 2, 3, 4-tetrahydroquinoxalinyl, etc.), quinazolinyl, dihydroquinazolinyl (e.g., 1, 4 (or 3, 4) -dihydroquinazolinyl, etc.), tetrahydroquinazolinyl (1, 2, 3, 4-tetrahydroquinazolinyl, etc.), cinnolinyl, pteridinyl, pyrazinopyridazinyl (e.g., pyrazino [ 2, 3-d ] pyridazinyl, etc.), imidazotriazinyl (e.g., imidazo [ 1, 2-b ] 1, 2, 4 ] triazinyl, etc.), imidazopyrazinyl (e.g., 1H-imidazo [ 4, 5-b ] pyrazinyl, etc.), imidazopyrimidinyl (e.g., 3H-purine, imidazo [ 1, 5-a ] (or [ 3, 4-a ])) pyrimidinyl, etc.), imidazopyridazinyl (e.g., imidazo [ 2, 3-b ] (or [ 3, 4-b ]) pyridazinyl, etc.), 1H-1- (or 2) azoindenyl, etc.

A saturated or unsaturated 7-to 12-membered (more preferably 8-to 10-membered) polycyclic (more preferably bicyclic) heterocyclic group containing 1 to 3 oxygen atoms.

Specific examples thereof include benzofuranyl group (e.g., benzo [ b ] (or [ c ]) furanyl group, etc.), isobenzofuranyl group, furopyridinyl group, benzopyranyl group (e.g., 2H-benzopyranyl group, etc.), chromanyl group, isochromanyl group, benzoxepin group (e.g., 3-benzoxepin group), cyclopentapyranyl group (e.g., cyclopenta [ b ] pyranyl group, etc.), furopyranyl group (e.g., 2H-furo [ 3, 2-b ] pyranyl group, etc.).

A saturated or unsaturated 7-to 12-membered (more preferably 8-to 10-membered) polycyclic (more preferably bicyclic) heterocyclic group containing 1 to 3 sulfur atoms.

Specific examples thereof include benzothienyl (e.g., benzo [ b ] thienyl, etc.), dihydrodithranyl (e.g., 4H-1, 3-dithranyl, etc.), dithranyl (e.g., 1, 4-dithranyl, etc.), etc.

A saturated or unsaturated 7-to 12-membered (more preferably 8-to 10-membered) polycyclic (more preferably bicyclic) heterocyclic group containing 1 to 3 nitrogen atoms and 1 to 2 oxygen atoms.

Specific examples thereof include a dioxoimidazolyl group (e.g., a 4H-1, 3-dioxolo [ 4, 5-d ] imidazolyl group), a benzoxazinyl group (e.g., a 4H-3, 1-benzoxazinyl group), a pyridooxazinyl group (e.g., a 5H-pyrido [ 2, 3-d ] oxazinyl group), a pyrazoloxazinyl group (e.g., a 1H-pyrazolo [ 4, 3-d ] oxazinyl group), and a furopyridyl group.

A saturated or unsaturated 7-to 12-membered (more preferably 8-to 10-membered) polycyclic (more preferably bicyclic) heterocyclic group containing 1 to 3 nitrogen atoms and 1 to 2 sulfur atoms.

Specific examples thereof include thienoimidazolyl (e.g., thieno [ 2, 3-d ] imidazolyl), thienopyridyl, dithiadiazadiindanyl (e.g., 2, 3-dithia-1, 5-diaza-indanyl), and the like.

A saturated or unsaturated 7-to 12-membered (more preferably 8-to 10-membered) polycyclic (more preferably bicyclic) heterocyclic group containing 1 to 3 oxygen atoms and 1 to 2 sulfur atoms.

Specific examples thereof include thienofuryl (e.g., thieno [ 2, 3-b ] furyl, etc.), etc.

A saturated or unsaturated 7-to 12-membered (more preferably 8-to 10-membered) polycyclic (more preferably bicyclic) heterocyclic group containing 1 nitrogen atom, 1 oxygen atom and 1 sulfur atom.

Specific examples thereof include an oxathiolanylpyrrolyl group (e.g., a 4H [ 1, 3 ] -oxathiolane [ 5, 4-b ] pyrrolyl group) and the like.

A saturated or unsaturated 7-to 12-membered (more preferably 8-to 10-membered) polycyclic (more preferably bicyclic) heterocyclic group containing 1 to 2 selenium atoms.

Preferable specific examples thereof include a benzoselenophenyl group (e.g., benzo [ b ] (or [ c ]) benzoselenophenyl group, etc.).

A saturated or unsaturated 7 to 12 (more preferably 8 to 10) polycyclic (more preferably bicyclic) heterocyclic group containing 1 to 2 selenium atoms and 1 to 3 nitrogen atoms.

Specific examples thereof include selenophenylpyridinyl (e.g., selenopheno [ 3, 2-b ] pyridyl), etc.

Preferable examples of the "lower alkylene group" include methylene, ethylene, propylene, butylene, pentylene, hexylene and the like, and an alkylene group having not more than 4 carbon atoms is particularly preferable.

Further, preferable examples of the "lower alkenylene group" include vinylene, 1-propenylene, 2-propenylene, 1-butenylene, 2-butenylene, 3-butenylene, 1-pentenylene, 2-pentenylene, 3-pentenylene, 4-pentenylene, 1-hexenylene, 2-hexenylene, 3-hexenylene, 4-hexenylene, 5-hexenylene and the like, and particularly preferred is alkenylene having not more than 4 carbon atoms.

The lower alkylene moiety of "oxa lower alkylene", "lower alkyleneoxy", "imino lower alkylene", "lower alkyleneimino", "thia lower alkylene" and "lower alkylenethia" is the same as the above alkylene.

"lower alkanoyl" is a straight-or branched-chain alkylcarbonyl group having not more than 6 carbon atoms. Preferred examples thereof include acetyl, propionyl, n-butyryl, isobutyryl, valeryl, isovaleryl, sec-butylcarbonyl, tert-butylcarbonyl, n-pentylcarbonyl, isopentylcarbonyl, sec-pentylcarbonyl, tert-pentylcarbonyl, and 2-methylbutylcarbonyl.

More preferably an alkanoyl group having not more than 4 carbon atoms.

"lower alkoxy" is a straight or branched chain alkyloxy group having not more than 6 carbon atoms. Preferred examples thereof include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, sec-pentoxy, tert-pentoxy, 2-methylbutoxy, n-hexoxy, isohexoxy, tert-hexoxy, sec-hexoxy, 2-methylpentoxy, 3-methylpentoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1-dimethylbutoxy, 2-dimethylbutoxy, 3-dimethylbutoxy, and 1-ethyl-1-methylpropoxy.

More preferred is an alkoxy group having not more than 4 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, and the like.

"heterocyclic lower alkyl" is a lower alkyl substituted by a "heterocyclic group" as defined above.

The "halogen atom" is, for example, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom.

Examples of the substituted amino group in the "substituted amino group" and "amino group which may be substituted" include lower alkanoylamino, mono-lower alkylamino, di-lower alkylamino, N-lower alkyl-N-acylamino, lower alkylsulfonylamino, aryl-lower alkylamino, N-heterocyclic-N-lower alkylamino, arylsulfonylamino, arylcarbonylamino and the like. N-lower alkyl-N-acylamino, for example, N-lower alkyl-N- (arylcarbonyl) amino, etc.

"lower alkanoylamino" is a substance in which the amino group is substituted with "lower alkanoyl" as defined above.

"Mono-or di-lower alkylamino" is an amino group substituted by a straight-or branched-chain alkyl group having not more than 6 carbon atoms. Preferred examples are methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino, n-pentylamino, isopentylamino, sec-pentylamino, tert-pentylamino, 2-methylbutylamino, n-hexylamino, 1-methylpentylamino, 2-methylpentylamino, 3-methylpentylamino, 4-methylpentylamino, 1-ethylbutylamino, 2-ethylbutylamino, 3-ethylbutylamino, 1-dimethylbutylamino, 2-dimethylbutylamino, 3-dimethylbutylamino and 1-ethyl-1-methylpropylamino.

More preferably an alkylamino group having not more than 4 carbon atoms, such as methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino, etc.

Preferred "acyl" of "N-lower alkyl-N-acylamino" is, for example, carbamoyl, aliphatic acyl, acyl with heterocycle called aromatic acyl, and acyl with heterocycle called heterocyclic acyl, etc.

Preferable examples of the acyl group include carbamoyl; lower or higher (having 7 or more carbon atoms, preferably 7 to 25 carbon atoms) alkanoyl groups such as formyl, acetyl, propionyl, butyryl, 2-methylpropionyl, pentanoyl, 2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, eicosanoyl and the like; lower or higher alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, tert-pentyloxycarbonyl, heptyloxycarbonyl and the like; lower or higher alkylsulfonyl such as methylsulfonyl, ethylsulfonyl and the like; lower or higher alkoxysulfonyl group and the like aliphatic acyl groups such as methoxysulfonyl group, ethoxysulfonyl group and the like; aroyl such as benzoyl, toluyl, naphthoyl and the like; phenyl (lower) alkanoyl such as phenylacetyl, phenylpropionyl, phenylbutyryl, phenylisobutyryl, phenylpentanoyl, phenylhexanoyl and the like; aryl (lower) alkanoyl such as naphthyl (lower) alkanoyl such as naphthylacetyl, naphthylpropionyl, naphthylbutyryl and the like; phenyl (lower) alkenoyl groups such as phenylpropenoyl, phenylbutenoyl, phenylmethacryloyl, phenylpentenoyl, phenylhexenoyl and the like; aryl (lower) alkenoyl groups such as naphthyl (lower) alkenoyl groups including naphthylacryloyl, naphthylcrotonyl and naphthylpentenoyl; aryl (lower) alkoxycarbonyl such as phenyl (lower) alkoxycarbonyl such as benzyloxycarbonyl, etc.; aryloxycarbonyl groups such as phenoxycarbonyl, naphthyloxycarbonyl, and the like; aryloxy (lower) alkanoyl such as phenoxyacetyl, phenoxypropionyl and the like; arylcarbamoyl groups such as phenylcarbamoyl and the like; arylthiocarbamoyl groups such as phenylthiocarbamoyl group and the like; arylglyoxyloyl groups such as phenylglyoxyloyl, naphthylglyoxyloyl and the like; aromatic acyl groups such as arylsulfonyl groups such as benzenesulfonyl and p-toluenesulfonyl; a heterocyclic carbonyl group; heterocyclic (lower) alkanoyl groups such as thienylacetyl, thienylpropionyl, thienylbutyryl, thienylpentanoyl, thienylhexanoyl, thiazolylacetyl, tetrazolylacetyl and the like; heterocyclic (lower) alkenoyl groups such as heterocycleoacryloyl, heterocycleocrotonyl, heterocycleopentenoyl, heterocyclohexenoyl and the like; heterocyclic glyoxyl groups such as thiazolyl glyoxyl group, thienyl glyoxyl group and the like.

The preferable heterocyclic moiety of the above-mentioned "heterocyclic carbonyl group", "heterocyclic (lower) alkanoyl group", "heterocyclic (lower) alkenoyl group" and "heterocyclic glyoxyl group" means, more specifically, a saturated or unsaturated monocyclic or polycyclic heterocyclic group containing at least 1 hetero atom such as an oxygen atom, a sulfur atom, a nitrogen atom and the like, and particularly preferable heterocyclic groups are exemplified by those mentioned above.

The above-mentioned acyl moiety may have 1 to 10 identical or different suitable substituents, for example, halogen (e.g., fluorine, chlorine, bromine or iodine), hydroxyl, nitro, lower alkyl (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, etc.), amino, protected amino, heterocyclic moiety and lower alkyl moiety, as described above with reference to heterocyclic (lower) alkylamino, lower alkoxy (e.g., methoxy, ethoxy, propoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.), carboxyl, protected carboxyl, N-di (lower) alkylamino (lower) alkyl (e.g., N-dimethylaminomethyl, N-diethylaminomethyl, N-dipropylaminomethyl, N-dimethylaminoethyl, N-diethylaminoethyl, N-diethylaminoethyl, N, N-dipropylaminoethyl group, N-dimethylaminopropyl group, N-diethylaminopropyl group, N-dipropylaminopropyl group, N-dibutylaminomethyl group, N-dipentaminomethyl group, N-dihexylaminomethyl group, etc.), hydroxyimino (lower) alkyl group (e.g., hydroxyiminomethyl group, hydroxyiminoethyl group, hydroxyiminopropyl group, hydroxyiminobutyl group, hydroxyiminopentyl group, hydroxyiminohexyl group, etc.), arylimino (lower) alkyl group (e.g., phenyliminomethyl group, phenyliminoethyl group, phenyliminopropyl group, phenyliminobutyl group, phenyliminopentyl group, phenyliminohexyl group, etc.), acyl group (e.g., formyl group, acetyl group, propionyl group, butyryl group, pentanoyl group, etc.) or lower alkanoyl group, The lower alkyl moiety and the heterocyclic moiety may refer to hydroxy (lower) alkylheterocyclic (lower) alkyl, mono (or di or tri) halo (lower) alkyl, arylamino (e.g., phenylamino) groups as described above.

"lower alkylsulfonyl" and "lower alkylsulfinyl" are those wherein sulfonyl and sulfinyl are each substituted by "lower alkyl" as defined above.

"lower alkylthio" is a straight or branched alkylthio group having not more than 6 carbon atoms. Preferable examples are methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, n-pentylthio, isopentylthio, sec-pentylthio, tert-pentylthio, 2-methylbutylthio, n-hexylthio, isohexylthio, tert-hexylthio, sec-hexylthio, 2-methylpentylthio, 3-methylpentylthio, 1-ethylbutylthio, 2-ethylbutylthio, 1-dimethylbutylthio, 2-dimethylbutylthio, 3-dimethylbutylthio, 1-ethyl-1-methylpropylthio and the like.

More preferred is an alkylthio group having not more than 4 carbon atoms, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio and the like.

"Mono-or di-lower alkylcarbamoyl" is a substance wherein carbamoyl is mono-or di-substituted by "lower alkyl" as defined above.

The "haloalkyl group" is a linear or branched alkyl group having not more than 6 carbon atoms which is substituted with a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and is preferably a linear or branched alkyl group having not more than 6 carbon atoms which is substituted with a fluorine atom, a chlorine atom or a bromine atom. For example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, 1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 1, 2-difluoroethyl, 1, 2-dichloroethyl, 1, 2-dibromoethyl, 2, 2, 2-trifluoroethyl, pentafluoroethyl, 1-fluoropropyl, 1-chloropropyl, 1-bromopropyl, 2-fluoropropyl, 2-chloropropyl, 2-bromopropyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl, 1, 2-difluoropropyl, 1, 2-dichloropropyl, 1, 2-dibromopropyl, 2, 3-difluoropropyl, 2, 3-dichloropropyl, 2, 3-dibromopropyl, 3, 3, 3-trifluoropropyl, 2, 3, 3, 3-pentafluoropropyl, 2-fluorobutyl, 2-chlorobutyl, 2-bromobutyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, 4, 4, 4-trifluorobutyl, 2, 3, 3, 4, 4, 4-heptafluorobutyl, perfluorobutyl, 2-fluoropentyl, 2-chloropentyl, 2-bromopentyl, 5-fluoropentyl, 5-chloropentyl, perfluoropentyl, 2-fluorohexyl, 2-chlorohexyl, 2-bromohexyl, 6-fluorohexyl, 6-bromohexyl, perfluorohexyl, 2-fluoroheptyl, 2-chloroheptyl, perfluoropentyl, 2-chlorohexyl, perfluorohexyl, 2-chlorohexyl, 2-chloropentyl, 2-bromoheptyl, 7-fluoroheptyl, 7-chloroheptyl, 7-bromoheptyl, perfluoroheptyl, and the like.

Preferred examples of the "aryl lower alkyl group" include C such as benzyl, phenethyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl, naphthylmethyl, naphthylethyl, naphthylpropyl, naphthylbutyl, naphthylpentyl, naphthylhexyl and the like₆-C₁₀Aryl radical (C)₁-C₆) An alkyl group.

"aryl lower alkenyl" and "aryl lower alkoxy" are those wherein "lower alkenyl" and "lower alkoxy" as defined above are substituted with "aryl" as defined above, respectively.

The "protected carboxyl group" is preferably, for example, an esterified carboxyl group.

Preferred examples of the ester moiety of the esterified carboxyl group are lower alkyl esters such as methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, tert-butyl ester, pentyl ester, hexyl ester and the like, which may further have at least 1 suitable substituent, for example, acetoxymethyl ester, propionyloxymethyl ester, butyryloxymethyl ester, valeryloxymethyl ester, pivaloyloxymethyl ester, hexanoyloxymethyl ester, 1 (or 2) -acetoxyethyl ester, 1 (or 2 or 3) -acetoxypropyl ester, 1 (or 2 or 3 or 4) -acetoxybutyl ester, 1 (or 2) -propionyloxyethyl ester, 1 (or 2 or 3) -propionyloxypropyl ester, 1 (or 2) -butyryloxyethyl ester, 1 (or 2) -isobutyryloxyethyl ester, 1 (or 2) -pivaloyloxyethyl ester, 1 (or 2) -hexanoyloxyethyl ester, Lower alkanoyloxy (lower) alkyl esters such as isobutyryloxymethyl ester, 2-ethylbutyryloxymethyl ester, 3-dimethylbutyloyloxymethyl ester, and 1 (or 2) -valeryloxyethyl ester; lower alkylsulfonyl (lower) alkyl esters such as 2-methanesulfonylethyl ester and the like; mono (or di or tri) halo (lower) alkyl esters such as 2-iodoethyl ester, 2, 2, 2 trichloroethyl ester, etc.; lower alkoxycarbonyloxy (lower) alkyl esters such as methoxycarbonyloxymethyl, ethoxycarbonyloxymethyl, 2-methoxycarbonyloxyethyl, 1-ethoxycarbonyloxyethyl and 1-isopropoxycarbonyloxyethyl; benzofuranone subunit (lower) alkyl esters; or (5-lower alkyl-2-oxo-1, 3-dioxol-4-yl) (lower) alkyl esters such as (5-methyl-2-oxo-1, 3-dioxol-4-yl) methyl ester, (5-ethyl-2-oxo-1, 3-dioxol-4-yl) methyl ester, and (5-propyl-2-oxo-1, 3-dioxol-4-yl) ethyl ester; lower alkenyl esters such as vinyl esters and allyl esters; lower alkynyl esters such as ethynyl ester and propynyl ester; aryl (lower) alkyl esters which may have at least 1 suitable substituent(s) (e.g., benzyl ester, 4-methoxybenzyl ester, 4-nitrobenzyl ester, phenethyl ester, trityl ester, diphenylmethyl ester, di (methoxyphenyl) methyl ester, 3, 4-dimethoxybenzyl ester, 4-hydroxy-3, 5-di-tert-butylbenzyl ester, etc., (or di or tri) phenyl (lower) alkyl esters which may have at least 1 suitable substituent (s)); phenyl esters, 4-chlorophenyl esters, tolyl esters, tert-butylphenyl esters, ditolyl esters, tricresyl esters, isopropylphenyl esters and the like which may have at least 1 suitable substituent; cyclic lower alkyl esters such as cyclohexyl; benzofuranone esters and the like.

The nitrogen-containing heterocyclic group shown is, for example, a substance having a nitrogen atom in the above heterocyclic group.

Preferred examples of the object compound (I) include compounds having the following groups in the general formula (I) and pharmaceutically acceptable salts thereof.

R¹Represents an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, a cyclo-lower alkyl group which may be substituted, an aryl group which may be substituted or a heterocyclic group which may be substituted,

the substituents for substituting these groups are each independently selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkoxy, aryl, heterocyclo-loweralkyl, halogen, amino, substituted amino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carboxy, protected carboxy, carbamoyl, loweralkylcarbamoyl, nitro, halo-loweralkyl, arylloweralkyl, arylloweralkenyl, arylloweralkoxy, loweralkoxy substituted with substituted amino, cycloloweralkylloweralkoxy, cycloloweralkylloweralkyl, aryloxygrouralkyl, acyloxyaralkyl, hydroxyloweralkyl, mono-or di-loweralkylaminoloweralkyl, arylloweralkyloxyalkyl, arylthio-loweralkyl, heterocyclo-loweralkoxy, heterocyclic-loweralkyl, heterocyclic-substituted-, At least 1 of heteroepoxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

A represents a polycyclic heterocyclic group containing at least 1 hetero atom including an oxygen atom, a sulfur atom, a selenium atom and a nitrogen atom in addition to the benzimidazolyl group, the indolyl group, the 4, 7-dihydrobenzimidazolyl group and the 2, 3-dihydrobenzoxazinyl group, which heterocyclic group may be substituted with at least 1 selected from the group consisting of alkyl, oxygen, sulfur, halogen, lower alkoxy, lower alkylthio, cyclo-lower alkyl, amino which may be substituted, aryl, a heterocyclic group, lower alkylsulfonyl and lower alkylsulfinyl,

R²represents an aryl group which may be substituted, a heterocyclic group which may be substituted or a biphenyl group which may be substituted,

the substituents when these groups are substituted are independently selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkoxy, aryl, heterocyclo-loweralkyl, halogen, amino, substituted amino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carboxy, protected carboxy, carbamoyl, loweralkylcarbamoyl, nitro, halo-loweralkyl, arylloweralkyl, arylloweralkenyl, arylloweralkoxy, loweralkoxy substituted with substituted amino, cycloloweralkylloweralkoxy, cycloloweralkyl, aryloxygralkyl, acyloxyloweralkyl, hydroxyloweralkyl, mono-or di-loweralkylaminoloweralkyl, arylloweralkyloxyalkyl, arylthio-loweralkyl, heterocyclo-loweralkoxy, heterocyclic-loweralkoxy, and the like, At least 1 of heteroepoxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

Wherein, when A represents a 3H-imidazo [ 4, 5-b ] pyridyl group substituted with a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a biphenyl group substituted with a group other than tetrazolyl;

when A represents a quinolyl group substituted by a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a substituted biphenyl group,

the substituent when the above-mentioned aryl and heterocyclic groups are substituted is selected from the group consisting of alkyl, cyclo-lower alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocyclo-lower alkyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono-lower alkylcarbamoyl, di-lower alkylcarbamoyl, nitro, halogeno-lower alkyl, aryl-lower alkenyl, aryl-lower alkoxy, lower alkoxy substituted with substituted amino, cyclo-lower alkyl-lower alkoxy, cyclo-lower alkyl, aryloxy-lower alkyl, acyloxy-lower alkyl, hydroxy-lower alkyl, mono-or di-lower alkylamino-lower alkyl, aryl-lower alkoxy-lower alkyl, arylthio-lower alkyl, heterocyclo-lower alkoxy, heterocyclic-lower alkoxy, heterocyclic-lower alkyl, heterocyclic-substituted aryl, heterocyclic group, and the like, At least 1 of heteroepoxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

The substituent for the above-mentioned biphenyl group is selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkoxy, phenyl, heterocyclo-loweralkyl other than tetrazolylmethyl, halogen, amino, substituted amino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carbamoyl, loweralalkylcarbamoyl, loweralkylcarbamoyl, nitro, halogeno-loweralkyl, aryl-loweralkenyl, aryl-loweralkoxy, loweralkoxy substituted with substituted amino, cycloloweralkylloweralkoxy, cycloloweralkyl, aryloxygienyl-loweralkyl, hydroxy-loweralkyl, mono-or di-loweralkylamino-loweralkyl, arylloweralkyl, arylthioloweralkyl, heterocyclo-loweralkoxy, heterocyclo-loweralkyl, at least 1 of aryl lower alkylthio, aryl ureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted.

Among the above compounds, the compounds having the following groups in the general formula (I) and pharmaceutically acceptable salts thereof are particularly preferable.

R¹Represents an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, a cyclo-lower alkyl group which may be substituted, a phenyl group which may be substituted or a heterocyclic group which may be substituted,

the substituents when these groups are substituted are each independently selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkoxy, phenyl, heterocyclo-loweralkyl, halogen, amino, loweralkylacylamino, mono-loweralkylamino, di-loweralkylamino, N-loweralkyl-N-acylamino, loweralkylsulfonylamino, aryl-loweralkylamino, N-heterocyclyl-N-loweralkylamino, arylsulfonylamino, arylcarbonylamino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono-loweralalkylcarbamoyl, di-loweralkylcarbamoyl, nitro, halo-loweralkyl, arylloweralkyl, arylloweralkenyl, arylloweralkoxy, loweralkylacylamino-loweralkoxy, lower alkanoylamino-alkoxyl, lower alkoxyl, At least 1 member selected from the group consisting of mono-lower alkylamino lower alkoxy, di-lower alkylamino lower alkoxy, N-lower alkyl-N-acylamino lower alkoxy, lower alkylsulfonylamino lower alkoxy, aryl lower alkylamino lower alkoxy, N-heterocycle-N-lower alkylamino lower alkoxy, arylsulfonylamino lower alkoxy, arylcarbonylamino lower alkoxy, cyclo-lower alkyl, aryloxo lower alkyl, acyloxylower alkyl, hydroxylower alkyl, mono-or di-lower alkylamino lower alkyl, aryl lower alkoxy lower alkyl, arylthio lower alkyl, heterocycle lower alkoxy, heterocyclyloxylower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

A represents a bicyclic heterocyclic group represented by the following (A) to (I) which may be substituted with at least 1 selected from the group consisting of alkyl, oxygen, sulfur, halogen, lower alkoxy, lower alkylthio, cyclo-lower alkyl, amino, lower alkanoylamino, mono-lower alkylamino, di-lower alkylamino, N-lower alkyl-N-acylamino, lower alkylsulfonylamino, aryl-lower alkylamino, N-heterocycle-N-lower alkylamino, arylsulfonylamino, arylcarbonylamino, aryl, heterocyclic group, lower alkylsulfonyl and lower alkylsulfinyl, in addition to benzimidazolyl, indolyl, 4, 7-dihydrobenzimidazolyl and 2, 3-dihydrobenzoxazinyl,

wherein, when A represents a 3H-imidazo [ 4, 5-b ] pyridyl group substituted with a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a biphenyl group substituted with a group other than tetrazolyl;

when A represents a quinolyl group substituted by a lower alkyl group, R²Represents an optionally substituted phenyl group, an optionally substituted naphthyl group, an optionally substituted heterocyclic group or an optionally substituted biphenyl group,

the substituent for substituting the above-mentioned phenyl, naphthyl and heterocyclic groups is selected from the group consisting of alkyl, cyclo-lower alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocyclic lower alkyl, halogen, amino, lower alkanoylamino, mono-lower alkylamino, di-lower alkylamino, N-lower alkyl-N-acylamino, lower alkylsulfonylamino, aryl-lower alkylamino, N-heterocyclic-N-lower alkylamino, arylsulfonylamino, arylcarbonylamino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxyl, protected carboxyl, carbamoyl, mono-lower alkylcarbamoyl, di-lower alkylcarbamoyl, nitro, halogeno-lower alkyl, aryl-lower alkenyl, aryl-lower alkoxy, lower alkanoylamino-lower alkoxy, lower alkoxyalkoxy, lower alkoxysulfonyl, lower alkoxy, At least 1 member selected from the group consisting of mono-lower alkylamino lower alkoxy, di-lower alkylamino lower alkoxy, N-lower alkyl-N-acylamino lower alkoxy, lower alkylsulfonylamino lower alkoxy, aryl lower alkylamino lower alkoxy, N-heterocycle-N-lower alkylamino lower alkoxy, arylsulfonylamino lower alkoxy, arylcarbonylamino lower alkoxy, cyclo-lower alkyl, aryloxo lower alkyl, acyloxylower alkyl, hydroxylower alkyl, mono-or di-lower alkylamino lower alkyl, aryl lower alkoxy lower alkyl, arylthio lower alkyl, heterocycle lower alkoxy, heterocyclyloxylower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

The substituent for the above-mentioned substituted biphenyl group is selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkyloxy, phenyl, heterocyclic loweralkyl other than tetrazolylmethyl, halogen, amino, loweralkylacylamino, loweralkylamino, N-loweralkyl-N-acylamino, loweralkylsulfonylamino, aryl loweralkylamino, N-heterocyclic-N-loweralkylamino, arylsulfonylamino, arylcarbonylamino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carbamoyl, loweralkylcarbamoyl, di-loweralkylcarbamoyl, nitro, halogenated loweralkyl, arylloweralkyl, arylloweralkenyl, arylloweralkoxy, loweralkylacylamino-loweralkoxy, lower alkanoylamino-alkoxyaryl, lower alkoxyaryl, Mono-lower alkylamino lower alkoxy, di-lower alkylamino lower alkoxy, N-lower alkyl-N-acylamino lower alkoxy, lower alkylsulfonylamino lower alkoxy, aryl lower alkylamino lower alkoxy, N-heterocycle-N-lower alkylamino lower alkoxy, arylsulfonylamino lower alkoxy, arylcarbonylamino lower alkoxy, cyclo-lower alkyl, aryloxy lower alkyl, acyloxy lower alkyl, at least 1 of hydroxy lower alkyl, mono-or di-lower alkylamino lower alkyl, aryl lower alkoxy lower alkyl, arylthio lower alkyl, heterocyclic lower alkoxy, heterocyclic oxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted.

The heterocyclic group is a heterocyclic ring represented by the following (A) to (T).

(A) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 4 nitrogen atoms

(B) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 3 oxygen atoms

(C) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 3 sulfur atoms

(D) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 3 nitrogen atoms and 1 to 2 oxygen atoms

(E) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 3 nitrogen atoms and 1 to 2 sulfur atoms

(F) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 2 oxygen atoms and 1 to 2 sulfur atoms

(G) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 nitrogen atom, 1 oxygen atom and 1 sulfur atom

(H) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 2 selenium atoms

(I) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 2 selenium atoms and 1 to 3 nitrogen atoms

(J) Unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atoms

(K) Saturated 3-to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atoms

(L) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms

(M) a saturated 3-to 8-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms

(N) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms

(O) a saturated 3-to 8-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms

(P) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 2 sulfur atoms

(Q) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 2 oxygen atoms

(R) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 oxygen atom

(S) spiroheterocyclic group containing 1 to 2 oxygen atoms

(T) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 oxygen atom and 1-2 sulfur atoms

Among the above compounds, preferred compounds of the formula (I) are those wherein A is selected from the group consisting of 2, 3-dihydrobenzimidazolyl, pyrazolopyrimidyl, tetrahydropyrazolopyrimidyl, imidazopyrazolyl, dihydroimidazopyrazole, imidazopyridyl, pyrrolopyridinyl, pyrazolopyridyl, benzopyrazolyl, dihydrobenzimidazolyl, benzotriazolyl, indolizinyl, isoindolyl, indazolyl, dihydroindolyl, isoindolyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthylamino, quinoxalyl, dihydroquinoxalyl, tetrahydroquinoxalyl, quinazolinyl, dihydroquinazolinyl, tetrahydroquinazolinyl, cinnolinyl, pteridinyl, pyrazinopyridazinyl, imidazotriazinyl, imidazopyrazinyl, imidazopyridyl, imidazopyrimidinyl, imidazopyridazinyl, 1H-1- (or 2) pyridazinyl, benzofuranyl, mehtyl, and mixtures thereof, Isobenzofuranyl, furopyridinyl, benzopyranyl, chromanyl, isochromanyl, benzoxepinatrienyl, cyclopentopyranyl, furopyranyl, benzothienyl, dihydrodithianyl, dithianyl, dioxonoimidazolyl, benzoxazinyl, pyridooxazinyl, pyrazolooxazinyl, furopyridinyl, thienoimidazolyl, thienopyridinyl, dithiadiazadihydroindenyl, thienofuranyl, oxathiolanylpyrrolopyrrolyl (oxathiolopyrryl), benzoselenophenyl, selenophenopyridinyl, benzoselenobizolyl (benzoselenol), selenophenopyridinyl and cyclopentopyridinyl, and these heterocyclic groups may also be substituted with lower alkyl and/or carbonyl groups.

Further, among the above compounds, the following compounds can be mentioned, and R in the general formula (I)¹Represents alkyl, alkenyl, phenyl lower alkenyl, nitro, phenyl which may be substituted by a substituent selected from alkyl and alkenyl, thienyl or quinquiA quinoline group,

a is a heterocyclic group selected from the group consisting of 2, 3-dihydrobenzimidazolyl, imidazopyrazolyl, imidazopyridinyl, pyrrolopyridinyl, pyrazolopyridinyl, benzotriazolyl, indolizinyl, indazolyl, quinolyl, dihydroquinoxalyl, tetrahydroquinoxalyl, dihydroquinazolinyl, tetrahydroquinazolinyl, benzofuranyl, benzothienyl and thienoimidazolyl, and these heterocyclic groups may also be substituted by lower alkyl and/or oxygen,

x is lower alkylene, oxo-lower alkylene or oxygen,

R²is alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, imidazolyl lower alkyl, piperidinyl lower alkyl, halogen, amino, lower alkanoylamino, mono-lower alkylamino, di-lower alkylamino, N-lower alkyl-N-lower alkanoylamino, N-lower alkyl-N-benzoylamino, lower alkylsulfonylamino, phenyl lower alkylamino, phenylsulfonylamino, benzoylamino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, lower alkoxycarbonyl, cyclo-lower alkylcarbonyloxy, mono-lower alkylcarbamoyl, nitro, halo-lower alkyl, phenyl lower alkenyl, phenyl lower alkoxy, (N-pyridyl-N-lower alkylamino) lower alkoxy, nitro, halo-lower alkyl, phenyl lower alkenyl, phenyl lower alkoxy, cyclo lower alkyl lower alkoxy, cyclo lower alkyl, phenoxy lower alkyl, lower alkylsulfonyloxy lower alkyl, hydroxy lower alkyl, di lower alkylamino lower alkyl, phenyl lower alkoxy lower alkyl, phenylsulphur lower alkyl, thienyl lower alkoxy, pyridyloxy lower alkyl, phenyl lower alkylthio, phenylureido, lower alkoxy, phenyl lower alkynyl, dioxothiazolidinylidene lower alkyl, substituted phenyl (the substituent being selected from thienyl which may be substituted by halogen), naphthyl which may be substituted by halogen, 4-phenylphenyl which may be substituted by halogen, thienyl which may be substituted by halogen, benzothienyl which may be substituted by halogen, quinolyl which may be substituted by halogen or benzotetrakis which may be substituted by halogen A hydrofuranyl compound.

Further, among the above compounds, the following compounds may be mentioned, R in the general formula (I)¹Represents alkyl, alkenyl, phenyl lower alkenyl, phenyl which may be substituted by a substituent selected from the group consisting of alkyl and alkenyl, thienyl which may be substituted by halogen,

a is a heterocyclic group selected from the group consisting of 3H-imidazo [ 4, 5-b ] pyridyl, pyrazolo [ 1, 5-a ] pyridyl, indolizinyl, 1H-indazolyl, benzo [ b ] furyl and benzo [ b ] thienyl, and these heterocyclic groups may also be substituted by 1 to 2 alkyl groups,

x is a lower alkylene group,

R²and a compound which is an alkyl group, a lower alkoxy group, a phenyl group, a halogen group, a di-lower alkylamino group, a lower alkylthio group, a lower alkoxycarbonyl group, a nitro group, a halogeno-lower alkyl group, a phenyl-lower alkenyl group, a phenyl-lower alkoxy group, a cyclo-lower alkyl-lower alkoxy group, a phenoxy-lower alkyl group, a phenyl-lower alkoxy-lower alkyl group, and a phenyl group which may be substituted (the substituent is selected from the group consisting of a thienyl group which may be substituted by a halogen group), a naphthyl group which may be substituted by a halogen group.

Among the above compounds, preferred are sulfonamide compounds wherein A is a 3H-imidazo [ 4, 5-b ] pyridyl group, 1H-indazolyl group or benzo [ b ] furyl group, which heterocyclic groups may be substituted with alkyl groups, or salts thereof, and R is ²Is phenyl substituted by halogen, which phenyl may also be substituted by substituents selected from the group consisting of alkyl, alkenyl, alkynyl, lower alkoxy, phenyl, halogen, di-lower alkylamino, lower alkylthio, lower alkoxycarbonyl, nitro, halo-lower alkyl, phenyl-lower alkenyl, phenyl-lower alkoxy, cyclo-lower alkyl-lower alkoxy, phenoxy-lower alkyl, phenyl-lower alkoxy-lower alkyl, phenyl-lower alkynyl and thienyl which may be substituted by halogen, or R²Is naphthyl substituted by halogen. Wherein preferably A is 3H-imidazo substituted by 1 or 2 lower alkyl groups[ 4, 5-b ] pyridyl, 1H-indazolyl substituted with 1 lower alkyl group and a-benzo [ b ] furyl substituted with 1 lower alkyl group.

Among them, particularly preferred groups are listed below.

R¹: phenyl, 2-nitrophenyl, o-or p-tolyl, n-pentenyl, n-butyl, n-pentyl, n-hexyl, thienyl, 8-quinolyl, (E) -2-phenylethenyl, 4-pentenyl, 4-vinylphenyl, 5-chlorothien-2-yl, 5-bromothien-2-yl, 4-ethylphenyl,

x: methylene group, -OCH ₂-, oxygen

R²: 2, 4-dichlorophenyl group, 2-chlorophenyl group, 4-bromo-2-chlorophenyl group, 2, 4-dichloro-5-fluorophenyl group, 3, 4-dichlorophenyl group, 2, 3-dichlorophenyl group, 2, 5-dichlorophenyl group, 2-bromo-4-chlorophenyl group, 4-chloro-2-methoxyphenyl group, 4-chloro-2-methylphenyl group, 4-phenylphenyl group, 2-chloro-4-phenylphenyl group, 1-bromo-2-naphthyl group, 3-chlorobenzo [ b ] thiophen-2-yl group, 2-chloro-4- (thiophen-2-yl) phenyl group, 2-chloro-4- (5-chlorothien-2-yl) phenyl group, 2-bromo-2-chlorophenyl group, 2-chloro-4- (thiophen-2-yl) phenyl group, 2-chloro-4-ethylphenyl, 2-chloro-4-vinylphenyl, 2-chloro-4-methylphenyl, 2-chloro-4- (N-pentyl) phenyl, 2-chloro-4- (isobutyl) phenyl, 2-chloro-4- (cyclohexylmethyl) phenyl, (E) -2-chloro-4- (2-phenylvinyl) phenyl, 4-benzyloxy-2-chlorophenyl, 2-chloro-4-methoxyphenyl, 2-chloro-4-isopropoxyphenyl, 2-chloro-4- (N-butoxy) phenyl, 2-chloro-4- ((cyclohexylmethyl) oxy) phenyl, 2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) Amino) ethyl) oxy) phenyl, 2-chloro-4- (methylthio) phenyl, 2-chloro-4- (methylsulfinyl) phenyl, 2-chloro-4- (methylsulfonyl) phenyl, 4- (benzylamino) -2-chlorophenyl, 4- (N-butylamino) -2-chlorophenyl, 2-chloro-4- (N, N-dimethylamino) phenyl, 4-acetylamino-2-chlorophenyl, 2-chloro-4- (methylsulfonylamino) phenyl, 2-chloro-4-nitrophenyl, 2-chloro-4-formylphenyl, 2-chloro-4- [ (2, 4-dioxo-1, 3-thiazolidin-5-ylidene) methyl ] phenyl, m, 2-chloro-4-fluorophenyl, 2, 4, 6-trichlorophenyl, 2, 3, 4-trichlorophenyl, 2-chloro-4-iodophenyl, 2, 5-dichlorothiophen-3-yl, 2-chloro-4, 5- (methylenedioxy) phenyl 2-chloroquinolin-3-yl, 2-chloro-4- (trifluoromethyl) phenyl, 2-chloro-4-cyanophenyl, 2-chloro-4- (2-phenylethyl) phenyl, 2-chloro-4-aminophenyl, 2-chloro-4- (hydroxymethyl) phenyl, 4-carboxy-2-chlorophenyl, 2-chloro-4- ((methylsulfonyloxy) methyl) phenyl, 2-chloro-4- ((phenoxy) methyl) phenyl, 2-chloro-4- (ethoxycarbonyl) phenyl, 2-chloro-4- (methylcarbamoyl) phenyl, 2-chloro-4- (dimethylaminomethyl) phenyl, 2-chloro-4- ((imidazol-1-yl) methyl) phenyl, 2-chloro-4- (trifluoromethyl) phenyl, and mixtures thereof, 2-chloro-4- ((piperidin-1-yl) methyl) phenyl, 2-chloro-4- (phenylthiomethyl) phenyl, 4- ((benzyloxy) methyl) -2-chlorophenyl, 4- (benzimidazol-2-yl) -2-chlorophenyl, 4- (1-methylbenzimidazol-2-yl) -2-chlorophenyl, 1-ethylbenzimidazol-2-yl, 2-chloro-4- (N-pentylthio) phenyl, 4- (benzylthio) -2-chlorophenyl, 2-chloro-4- ((3-piperidinyloxy) methyl) phenyl, 2-chloro-4-ethylthiophenyl, 4- (N-butyrylamino) -2-chlorophenyl, methyl-o-benzoxy-l, methyl, 4- (N-benzoylamino) -2-chlorophenyl, 4- (N-benzoyl-N-methylamino) -2-chlorophenyl, 4- (N-butyryl-N-methylamino) -2-chlorophenyl, 2-chloro-4- (N-N-pentylamino) phenyl, 2-chloro-4- (N-methyl-N-N-pentylamino) phenyl, 4- (N-benzenesulfonylamino) -2-chlorophenyl, 2-chloro-4- (isopropoxycarbonyl) phenyl, 2-chloro-4- (cyclohexyloxycarbonyl) phenyl, 2-chloro-4- (3-phenylureido) phenyl, 2-chloro-4-propoxyphenylamino, N-phenylthio, N-methyl-N-methylamino) -2-chlorophenyl, N-butyryl-2-chlorophenyl, N-propylthio, 2-chloro-4-n-pentyloxyphenyl, 2-chloro-4-ethoxyphenyl, 2-chloro-4- (2-methoxyethoxy) phenyl, 2-chloro-4- [ (thien-2-yl) methoxy ] phenyl, 2-chloro-4- [ (thien-3-yl) methoxy ] phenyl, 2-chloro-4-phenylethynylphenyl, 2-chloro-4- (cyclopentylmethoxy) phenyl, 2-chloro-4- (1-hexynyl) phenyl, 2-chloro-4-hexylphenyl, 2-chloro-4-piperidinophenyl, 2-chloro-4-morpholinophenyl, 2-chloro-4- (hexamethyleneamino) phenyl, p-tolyl-amino-methyl-p-toluenesulfonyl-ethyl, p-tolyl-methyl-p-toluenesulfonyl, p-toluenesulfonyl-methyl-2-4-aminobutyl, 2-chloro-4-pyrrolidinophenyl, 2-chloro-4- (4-methylpiperazin-1-yl) phenyl

A: 4H-imidazo [ 1, 2-b ] pyrazolyl, 3H-thieno [ 2, 3-d ] imidazolyl, 1H-thieno [ 2, 3-d ] imidazolyl, imidazo [ 1, 2-a ] pyridyl, 1H-pyrrolo [ 3, 2-b ] pyridyl, 2, 3-dihydrobenzo [ d ] imidazolyl, 1H-indazolyl, indolizinyl, benzotriazolyl, 1H-imidazo [4, 5-b ] pyridyl, 3H-imidazo [4, 5-b ] pyridyl, pyrazolo [ 1, 5-a ] pyridyl, benzo [ b ] furyl, benzo [ b ] thienyl, 3, 4-dihydroquinazolinyl, 1, 2-dihydroquinoxalinyl, 1, 2, 3, 4-tetrahydroquinoxalinyl, quinolyl, pyridyl, and the like, 1, 2, 3, 4-tetrahydroquinazolinyl, 1, 4-dihydroquinazolinyl, 2H-indazolyl

A substituent group: methyl, ethyl, n-propyl, oxygen

Preferred specific examples of the object compound (I) are shown below. 3- (3, 4-Dichlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen-3- (2, 3-dichlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen-3- (2, 5-dichlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen-3- (2, 4-dichlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) pyrazolo [ 1, 5-a ] pyridine-3- (2, 4-dichlorophenylmethyl) -2-methyl-5- (benzenesulfonylcarbamoyl) pyrazolo [ 1, 5-a ] pyridinyle 1- (2, 4-dichlorobenzyl) -2-methyl-7- (n-pentylsulfonylcarbamoyl) indolizine 7-n-butylsulfonylcarbamoyl-1- (2, 4-dichlorobenzyl) -2-methylindolizine 1- (2, 4-dichlorobenzyl) -2-methyl-7- (benzenesulfonylcarbamoyl) indolizine 2-methyl-7- (n-pentylsulfonylcarbamoyl) -1- (4-phenylbenzyl) indolizine 6- (n-pentylsulfonylcarbamoyl) -4- (4-phenylbenzyl) quinolineformyl 3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazole And [4, 5-b ] pyridin5- (n-butylsulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin5-benzenesulfonylcarbamoyl-3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (1-bromo-2-naphthyl) methyl-2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 2-methyl-5- (n-pentylsulfonylcarbamoyl) -3- (4-phenylbenzyl) -3H-imidazo [4, 5-b ] pyridinato 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (4-bromo-2-chlorophenylmethyl) -5- (n-butylsulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- (benzenesulfonylcarbamoyl) -3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny-3- (2-bromo-4-chlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-5- (benzenesulfonylcarbamoyl) -3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny-3- (2-bromo-4-chloromethyl) -5- (n-butylsulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny-3- (2, 4-dichlorobenzyl) -2-methyl-6- (n-pentylsulfonylcarbamoyl) indolizine-3- (2, 4-Dichlorophenylmethyl) -2-methyl-6- (n-butylsulfonylcarbamoyl) indolizine 3- (2, 4-dichlorobenzyl) -2-methyl-6- (benzenesulfonylcarbamoyl) indolizine 3- (2, 4-dichlorobenzyl) -2-ethyl-7-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridine 2-ethyl-7-methyl-5- (n-pentylsulfonylcarbamoyl) -3- (4-phenylbenzyl) -3H-imidazo [4, 5-b ] pyridine 3- (2, 4-dichlorobenzyl) -2-methyl-5- (benzenesulfonylcarbamoyl) benzo [ ] b ] thiophen.3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-butylsulfonylcarbamoyl) benzo [ b ] thiophen.3- (4-phenylbenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen.3- (2-chlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen.3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen.3- (2, 4-dichloro-5-fluorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen.3- ((3-chlorosulfonylcarbamoyl) Benzo [ b ] thiophen-2-yl) methyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen-3- (1-bromonaphthalen-2-yl) methyl-2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen-1- (2, 4-dichlorobenzyl) -2-methyl-5-n-pentylsulfonylcarbamoyl-1H-thieno [ 2, 3-d ] imidazoie-3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-thieno [ 2, 3-d ] imidazoie-1- (2, 4-dichlorobenzyl) -2-methyl-6- (n-pentylsulfonylcarbamoyl) Acyl) -1H-imidazo [4, 5-b ] pyridinato 3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) pyrrolo [ 3, 2-b ] pyridinato 3- (2, 4-dichlorobenzyl) -2-methyl-5- (benzenesulfonylcarbamoyl) pyrrolopyridinato 3- (4-chloro-2-methoxybenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (4-chloro-2-methylbenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinylcarbamoyl-3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinylcarbamoyl-5-benzenesulfonylcarbamoyl-3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazole [4, 5-b ] pyridinylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinylcarbamoyl-3- (2, 4-dichlorobenzyl) -2-methyl-5- (1-n-pentylsulfonylcarbamoyl) benzo [ b ] furazan-5- (benzenesulfonyl) carbamoyl Alkylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan.2- (2, 4-dichlorobenzyl) -3, 5-dimethyl-7- (1-n-pentylsulfonylcarbamoyl) benzo [ b ] furan.7- (benzenesulfonylcarbamoyl) -2- (2, 4-dichlorobenzyl) -3, 5-dimethylbenzo [ b ] furan.2-methyl-5- (1-n-pentylsulfonylcarbamoyl) -3- (4-phenylbenzyl) benzo [ b ] furan.5- (1-benzenesulfonylcarbamoyl) -2-methyl-3- (4-phenylbenzyl) benzo [ b ] furan.5- (1-n-butylsulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan.3- (2, 4-dichlorobenzyl) -5- (1-n-hexylsulfonylcarbamoyl) -2-methylbenzo [ b ] furan.3- (2, 4-dichlorobenzyl) -2-methyl-5- (2-thiophenesulfonylcarbamoyl) benzo [ b ] furan.3- (2, 4-dichlorobenzyl) -2-ethyl-5- (1-n-pentylsulfonylcarbamoyl) benzo [ b ] furan.5- (benzenesulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-ethylbenzo [ b ] furan.3- (2, 4-Dichlorophenylmethyl) -2-ethyl-5- (8-quinolinesulfonylcarbamoyl) benzo [ b ] furan.3- (2, 4-dichlorophenylmethyl) -2-ethyl-5- ((2-methylbenzene) sulfonylcarbamoyl) benzo [ b ] furan.3- (2, 4-dichlorophenylmethyl) -5- (1-n-pentylsulfonylcarbamoyl) -2-propylbenzo [ b ] furan.5- (benzenesulfonylcarbamoyl) -3- (2, 4-dichlorophenylmethyl) -2-propylbenzo [ b ] furan.3- (2, 4-dichlorophenylmethyl) -5-ethyl- (2-nitrobenzenesulfonylcarbamoyl) -2-propylbenzo [ b ] furan.3- (2, 4-Dichlorophenylmethyl) -5- (1-n-pentylsulfonylcarbamoyl) benzo [ b ] furan.3- (2, 4-dichlorophenylmethyl) -2-methyl-5- (1-n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene.2- (2, 4-dichlorophenylmethyl) -3-ethyl-7- (1-n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene.7- (benzenesulfonylcarbamoyl) -2- (2, 4-dichlorophenylmethyl) -3-ethylbenzo [ b ] thiophene.6- (1-n-butylsulfonylcarbamoyl) -1- (2, 4-dichlorophenylmethyl) -3-methyl-2-benzimidazolone.1- (2, 4-Dichlorobenzyl) -3-methyl-6- (1-pentanesulfonylcarbamoyl) -1H-indazol.6- (benzenesulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-methyl-1H-indazole (E) -1- (2, 4-dichlorobenzyl) -3-methyl-6- ((2-phenylvinyl) sulfonylcarbamoyl) -1H-indazol.6- (1-n-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) benzotriazol.6- (1-n-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-methyl-1H-indazole.7- (1-n-butylsulfonylcarbamoyl) -n-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-ethyl-4 (3H) -quinazolinone.7- (1-n-butylsulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -1-methyl-4 (3H) -quinazolinone.7- (1-n-butylsulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -4(3H) -quinazolinone.7- (1-n-butylsulfonylcarbamoyl) -2- (2, 4-dichlorobenzyl) -3-methyl-4 (3H) -quinazolinone.6- (1-n-butylsulfonylcarbamoyl) -3- (2, 4-Dichlorobenzyl) -3, 4-dihydro-2-methyl-quinazolinecar-chloride 1- (2, 4-dichlorobenzyl) -2-methyl-7- (1-n-pentanesulfonylcarbamoyl) -4(1H) -quinazolinone 7- (benzenesulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -2-methyl-4 (1H) -quinazolinone 1- (2, 4-dichlorobenzyl) -1, 4-dihydro-2-methyl-7- (1-n-pentanesulfonylcarbamoyl) quinazolinecar-chloride 7- (1-n-butylsulfonylcarbamoyl) -1- (2, 4-Dichlorobenzyl-3-methyl-2 (1H) -quinoxalinone.7- (1-n-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -4-methyl-2, 3- (1H, 4H) -quinoxalinedione.4- (2, 4-dichlorobenzyl) -5-ethyl-3- (1-n-pentylsulfonylcarbamoyl) imidazo [ 1, 2-b ] pyrazole.3- (2, 4-dichlorobenzyl) -2-methyl-6- (1-n-pentylsulfonylcarbamoyl) imidazo [ 1, 2-a ] pyridine.6- (n-pentylsulfonylcarbamoyl) -4- (4-phenylphenoxy) quinoline.6- (n-pentylsulfonylcarbamoyl) ) -4- (4-Phenylbenzyloxy) quinolinato 3- (2, 4-dichlorobenzyl) -2-ethyl-5- (((E) -pentene-1-sulfonyl) carbamoyl) benzo [ b ] furan 1- (2, 4-dichlorobenzyl) -3-ethyl-6- (1-n-pentanesulfonylcarbamoyl) -1H-indazol-6- (benzenesulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-ethyl-1H-indazol-6- (benzenesulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylimidazo [ 1, 2-a ] pyrid-ine 3- (2, 3-Dichlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methyl-5-n-pentylsulfonylcarbamoyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophen 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (((E) -1-pentene-1-sulfonyl) carbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 1- (2-chloro-4-phenylbenzyl) -3-methyl-6- (1-pentanesulfonylcarbamoyl) -1H-indazole 6- (benzenesulfonylcarbamoyl) -1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (E) -1- (2-chloro-4-phenylbenzyl) -3-methyl-6- ((2-phenylvinyl) sulfonylcarbamoyl) -1H-indazole 1- (2-chloro-4-phenylbenzyl) -3-methyl-6- (((E) -1-pentene-1-sulfonyl) carbamoyl) -1H- Indazole 1- (2-chloro-4-phenylbenzyl) -3-methyl-6- ((4-vinylbenzene) sulfonylcarbamoyl) -1H-indazole 1- (2-chloro-4-phenylbenzyl) -3-methyl-6- ((4-methylbenzene) sulfonylcarbamoyl) -1H-indazole 1- (4-bromo-2-chlorophenylmethyl) -3-methyl-6- (1-pentasulfonylcarbamoyl) -1H-indazole 6- (benzenesulfonylcarbamoyl) -1- (4-bromo-2-chlorophenylmethyl) -3-methyl-1H-indazole (E) -1- (4-bromo-2- Chlorobenzyl) -3-methyl-6- ((2-phenylvinyl) sulfonylcarbamoyl) -1H-indazole.3- (2, 4-dichlorobenzyl) -2-methyl-5- (((E) -1-pentene-1-sulfonyl) carbamoyl) benzo [ b ] furan (E) -3- (2, 4-dichlorobenzyl) -2-methyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) benzo [ b ] furan.3- (2, 4-dichlorobenzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) benzo [ b ] furan.3- (2-chloro-4-phenylbenzyl) -2-methyl- 5- (1-Pentanesulfonylcarbamoyl) benzo [ b ] furan.5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methylbenz [ b ] furan (E) -3- (2-chloro-4-phenylbenzyl) -2-methyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) benzo [ b ] furan.3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (4-vinylbenzenesulfonylcarbamoyl) benzo [ b ] furan.3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (((E) -1-pentene-1-sulfonyl) Carbamoyl) benzo [ b ] furan.3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) benzo [ b ] furan.5- (benzenesulfonylcarbamoyl) -3- (4-bromo-2-chlorophenylmethyl) -2-methylbenzo [ b ] furan (E) -3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) benzo [ b ] furan.3- (2, 4-dichlorobenzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine.3- (2, 4-dichlorobenzyl) -2-methyl-5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine (E) -3- (2, 4-dichlorobenzyl) -2-methyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine.5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine.5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2, 4-Dichlorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine (E) -3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine.3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine.3- (2-chloro-4-phenylbenzyl) -2-methyl-5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine [4, 5-b ] pyridine (E) -3- (2-chloro-4-phenylbenzylmethyl) -2-methyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine 3- (2-chloro-4-phenylbenzylmethyl) -5- [ (5-chlorothien-2-yl) sulfonylcarbamoyl ] -2-methyl-3H-imidazo [4, 5-b ] pyridine 3- (2-chloro-4-phenylbenzylmethyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine 5- [ (5-bromothien-2-yl) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzenyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 3- (2-chloro-4-phenylbenzenyl) -5- [ (4-ethylbenzene) sulfonylcarbamoyl ] -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- [ 2-chloro-4- (thien-2-yl) benzyl ] -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- [ 2- Chloro-4- (5-chlorothien-2-yl) benzyl ] -2-methyl-3H-imidazo [4, 5-b ] pyrid-ine.3- (2-chloro-4-ethylbenzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyrid-ine.5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyrid-ine.3- (2-chloro-4-ethylbenzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine (E) -3- (2-chloro-4-ethylbenzyl) -2-methyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-vinylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-methylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-n-pentylbenzyl) -one-shot 2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-isobutylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine (E) -5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin5- (benzenesulfonylcarbamoyl) -3- (4-benzyloxy-2-chlorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-methoxybenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin5- (benzenesulfonylcarbamoyl) -3- (4-n-butoxy-2-chlorobenzyl) -2-methyl-3 H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylsulfinyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (4- (benzylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (4- (n-butylamino) -2-chlorobenzyl) -one 2-methyl-3H-imidazo [4, 5-b ] pyridin5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (N, N-dimethylamino) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin3- (4- (acetylamino) -2-chlorobenzyl) -5- (benzenesulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylsulfonylamino) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- [ 2-chloro-4- [ (2, 4-dioxo-1, 3-thiazolidin-5-ylidene) methyl ] benzyl ] -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2- Chloro-4-fluorophenylmethyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -2-methyl-3- (2, 4, 6-trichlorophenylmethyl) -3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -2-methyl-3- (2, 3, 4-trichlorophenylmethyl) -3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (2, 4-dichloro-5-fluorophenylmethyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-substituted carboxylic acid 4-iodobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridino 5- (benzenesulfonylcarbamoyl) -3- ((2, 5-dichlorothien-3-yl) methyl) -2-methyl-3H-imidazo [4, 5-b ] pyridino 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridino 5- (benzenesulfonylcarbamoyl) -3- ((2-chloroquinolin-3-yl) methyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine 3- [ 2-chloro-4- (trifluoromethyl) benzyl ] -2-methyl-5- (1-pentylsulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridine 3- [ 2-chloro-4- (trifluoromethyl) benzyl ] -2-methyl-5- [ (4-methylbenzyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (1-bromonaphthalene-2- Ylmethyl) -2-methyl-3H-imidazo [4, 5-b ] pyridin3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- (pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin5- (benzenesulfonylcarbamoyl) -3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyridinE) -3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridine 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridine 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine (E) -3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine 3- (4-bromo-2-chlorophenylmethyl) -5- [ (5-chlorothien-2-yl) sulfonylcarbamoyl ] -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyridin-3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridin-3- (4-bromo-2-chlorophenylmethyl) -5- [ (5-bromothien-2-yl) sulfonylcarbamoyl ] -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyridine 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-5- ((4-methylbenzyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridine (E) -3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-cyanobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine (E) -3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 3- (2-chloro-4- (trifluoromethyl) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyrid-5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyrid-5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] thiophen-1- (2-chloro-4-phenylbenzyl) -6- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -3-methyl-1H- Indazol.6- ((5-bromothien-2-yl) sulfonylcarbamoyl) -1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazol.3- (1-bromonaphthalen-2-ylmethyl) -5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyridine.5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine.3- (4-amino-2-chlorophenylmethyl) -5- (benzenesulfonyl) carbamoyl Carbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (hydroxymethyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- (benzenesulfonylcarbamoyl) -3- (4-carboxy-2-chlorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((methylsulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylcarbamoyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2 -methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- (E) - (2-phenylvinyl) Benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridi-n.5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (E) - (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridi-n.3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (2-phenylethyl) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (4-benzyloxy-2-chlorophenylmethyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny-3- (4-benzyloxy-2-chlorophenylmethyl) -5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridiny-3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-5- (1-pentasulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (methylthio) benzyl) -2-methyl-5- ((4-methylbenzyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (methylthio) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (methylthio) benzyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (methylthio) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (methylthio) benzyl) -5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-5- [ (E) - (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- (dimethylaminomethyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- ((imidazol-1-yl) methyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- ((piperidin-1-yl) methyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 3- (2-chloro-4- (phenylthiomethyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 3- (4- ((benzyloxy) methyl) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 3- (4- (benzimidazol-2-yl) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin2-methyl-5- [ (4-methylbenzo) sulfonylcarbamoyl ] -3- [ 4- (1-methylbenzimidazol-2-yl) -2-chlorobenzyl ] -3H-imidazo [4, 5-b ] pyridin3- [ (1-ethylbenzimidazol-2-yl) methyl ] -2-methyl-5- [ (4-methylbenzo) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (thien-2-yl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (thien-2-yl) benzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (thien-2-yl) benzyl) -5- [ (5-chlorothien-2-yl) sulfonylcarbamoyl ] -2-methyl-3H-imidazo [4, 5-b ] pyridin5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (thien-2-yl) benzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-5- [ (E) - (2-phenylethene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -5- [ (5-chlorothien-2-yl) sulfonylcarbamoyl ] -2-methyl-3H-imidazo [4, 5-b ] pyridiny-5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-me Yl-3H-imidazo [4, 5-b ] pyrid-3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-5- [ (E) - (2-phenylethene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyrid-3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyrid-3- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H- Imidazo [4, 5-b ] pyridine.3- (2-chloro-4-phenylbenzenyl) -5- [ (5-chlorothien-2-yl) sulfonylcarbamoyl ] -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyridine.5- [ (5-bromothien-2-yl) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzenyl) -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyridine.3- (2-chloro-4-phenylbenzenyl) -2, 7-dimethyl-5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4 ], 5-b ] pyridin3- [ 2-chloro-4- (thien-2-yl) benzyl ] -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- [ 2-chloro-4- (thien-2-yl) benzyl ] -2, 7-dimethyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridin5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (thien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyridino 3- (2-chloro-4- (thien-2-yl) benzyl) -2, 7-dimethyl-5- [ (E) - (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridino 3- (2-chloro-4- (thien-2-yl) benzyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridino 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyrid-ine.3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyrid.5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [4, 5-b ] pyrid-ine.3- (2-chloro-4- (5-chlorothien-2-yl) Benzyl) -2, 7-dimethyl-5- [ (E) - (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridin-3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin-3- [ 2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine-3- [ 4- (benzylthio) -2-chloro ] benzyl-2 -methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridin-3- (2-chloro-4- ((3-pyridyloxy) methyl) benzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridin-3- (2-chloro-4-ethylsulfanylphenylmethyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridin-3- (4- (N-butyrylamino) -2-chloro-benzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine-3- (4- (N-butyrylamino) -2-chloro-benzyl) -2-methyl-5- [ (4-methylbenzene) sulfonyl- ] -3H-imidazo ) Sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyrid-ine.3- (4- (N-benzoylamino) -2-chloro-benzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyrid-ine.3- (4- (N-benzoyl-N-methylamino) -2-chlorophenylmethyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyrid-ine.5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyrid-ine 5-b ] Pyridinium sodium.5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzylmethyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinm sodium.5- [ (5-bromothien-2-yl) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzylmethyl) -2-methyl-3H-imidazo [4, 5-b ] pyridinm sodium.3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [4 ", 5-b ] Pyridinium sodium 3- (4- (N-butyryl-N-methylamino) -2-chlorophenylmethyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] Pyridinium 3- (2-chloro-4- (N- (N-pentyl) amino) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] Pyridinium 3- (2-chloro-4- (N-methyl-N- (N-pentyl) amino) benzyl) -2-methyl-5 [4, 5-b ] pyridinato 3- (4- (N-benzenesulfonylamino) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (isopropoxycarbonyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (cyclohexyloxycarbonyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (3-phenylureido) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4-propoxybenzylmethyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4- (n-pentyloxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridin3- (2-chloro-4-ethoxy) benzylcarbamoyl -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-l 3- (2-chloro-4- (2-methoxyethoxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-l 3- (2-chloro-4- ((thien-2-yl) methoxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-l 3- (2-chloro-4- ((thien-3-yl) methoxy) benzyl) -2- Methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4-phenylvinyl) benzyl-2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4- (cyclopentylmethoxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2-chloro-4-phenylvinyl) benzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (1-hexenyl) benzyl-2-methyl-5- (N- (4-methylbenzenesulfonyl) carbamoyl-3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (cyclohexylmethoxy) benzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (cyclohexylmethoxy) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyrid-ine 3- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-5- (1-pentasulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyrid-ine 3- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyrid-ine 3- (2-chloro-4- (trifluoromethyl) benzyl) -2, 7-dimethyl-5- (1-pentasulfonylcarbamoyl) -3H-imidazoie Azolo [4, 5-b ] pyridinato 3- (2-chloro-4- (trifluoromethyl) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4-ethoxybenzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4-ethoxybenzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridiny-3- (2, 4-dichlorobenzyl) -2-methyl-5- (p-toluenesulfonylcarbamoyl) benzo [ b ] fury-5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] fury-5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] fury-3- (2-chloro-4-phenylbenzyl) -2-methyl-5- ((4-pentene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 2- (2-chloro-4-phenylbenzyl) -3-methyl-6- (p-toluenesulfonylcarbamoyl) -2H-indazole 3- (2-chloro-4-hexylbenzyl) -2-methyl-5- (N- (4-methylbenzenesulfonyl) carbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 3- (2-chloro-4-piperidinobenzylmethyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinyle 3- (2-chloro-4-morpholinobenzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (hexamethyleneimino) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (1-pyrrolidinyl) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4- (4-methylpiperidin-1-yl) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato 3- (2-chloro-4-methylthiobenzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [4, 5-b ] pyridinato

The process for producing the object compound (I) is described in detail below. The preparation method comprises the following steps:

the object compound (I) or a salt thereof can be produced by reacting the compound (II) or a salt thereof with the compound (III) or a reactive derivative of a carboxyl group thereof or a salt thereof.

Suitable salts of the compounds (II) and (III) and the reactive derivative of the carboxyl group thereof are the same as those exemplified for the compound (I).

Suitable reactive derivatives at the carboxyl group of compound (III) are, for example, acid halides, anhydrides (including intramolecular, intermolecular and mixed anhydrides), activated amides, activated esters, and the like. Preferred examples of such reactive derivatives are acyl chlorides; an acyl azide; mixed acid anhydrides with acids such as substituted phosphoric acids (e.g., dialkyl phosphoric acid, phenyl phosphoric acid, diphenyl phosphoric acid, benzhydryl phosphoric acid, halogenated phosphoric acids, etc.), dialkyl phosphorous acid, sulfurous acid, thiosulfuric acid, sulfuric acid, sulfonic acids (e.g., methanesulfonic acid, etc.), aliphatic carboxylic acids (e.g., acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, valeric acid, isovaleric acid, 2-ethylbutyric acid, trichloroacetic acid, etc.), aromatic carboxylic acids (e.g., benzoic acid, etc.); a symmetric anhydride; an active amide with imidazole, 4-substituted imidazole, dimethylpyrazole, triazole or tetrazole; active esters (e.g. cyanomethyl, methoxymethyl, dimethyliminomethyl [ (CH) ₃)₂N⁺CH- ]ester, vinyl ester, propargyl ester, p-nitrophenyl ester, 2, 4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, methanesulfonylphenyl ester, phenylazophenyl ester, thiophenyl ester, p-nitrobenzylthio ester, p-tolylthio ester, carboxymethylthio ester, pyranyl ester, pyridyl ester, piperidyl ester, 8-quinolylthio ester, etc.) or an ester with an N-hydroxy compound (e.g., N-dimethylhydroxylamine, 1-hydroxy-2-1H-pyridone, N-hydroxysuccinimide, 1-hydroxy-1H-benzotriazole, etc.), etc. These reactive derivatives can be appropriately selected from them according to the kind of the compound (III) to be used.

The reaction is usually carried out in a conventional solvent such as water, alcohol (e.g., methanol, ethanol, etc.), acetone, dioxane, acetonitrile, chloroform, dichloromethane, dichloroethane, tetrahydrofuran, ethyl acetate, N-dimethylformamide, pyridine, any other solvent which does not adversely affect the reaction. These conventional solvents may be used alone or as a mixture.

In this reaction, when the compound (III) is used in the form of a free acid or a salt thereof, it is preferable to carry out the reaction in the presence of a conventional condensing agent such as N, N ' -dicyclohexylcarbodiimide, N-cyclohexyl-N ' -morpholinoethylcarbodiimide, N-cyclohexyl-N ' - (4-diethylaminocyclohexyl) carbodiimide, N ' -diethylcarbodiimide, N ' -diisopropylcarbodiimide, N-ethyl-N ' - (3-dimethylaminopropyl) carbodiimide, N ' -carbonylbis (2-methylimidazole), pentamethyleneenone-N-cyclohexylimine, diphenylenone-N-cyclohexylimine, ethoxyacetylene, 1-alkoxy-1-vinylchloride, diphenylketene-N-cyclohexylimine, 1-alkoxy-1-vinylchloride, or a salt thereof, Trialkyl phosphite, ethyl polyphosphate, isopropyl polyphosphate, phosphorus oxychloride, phosphorus trichloride, diphenylphosphoryl azide, diphenyl chlorophosphate, diphenylphosphinyl chloride, thionyl chloride, oxalyl chloride, lower alkyl haloformates (e.g., ethyl chloroformate, isopropyl chloroformate, etc.), triphenylphosphine, 2-ethyl-7-hydroxybenzoisoxazolium salt, 2-ethyl-5- (m-sulfophenyl) isoxazolium hydroxide intramolecular salt, 1- (p-chlorobenzenesulfonyloxy) -6-chloro-1H-benzotriazole, so-called Vilsmeier's reagent (prepared by reacting N, N-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, phosphorus oxychloride, etc.), and the like.

The reaction may be carried out in the presence of an inorganic or organic base such as an alkali metal hydrogencarbonate, tri-lower alkylamine, pyridine, 4-dimethylaminopyridine, N-lower alkylmorpholine, N-di-lower alkylaniline (e.g., N-dimethylaniline), N-di-lower alkylbenzylamine or the like.

The reaction temperature is not particularly limited, and the reaction is usually carried out under cooling or heating. The preparation method 2 comprises the following steps:

the object compound (I-2) or a salt thereof can be produced by reducing the compound (I-1) or a salt thereof.

When the objective compound (I-2) is obtained by reduction, methods thereof include, for example, chemical reduction and catalytic reduction.

Suitable reducing agents for chemical reduction such as metals like tin, zinc, iron, etc.; and combinations of metal compounds such as chromium chloride and chromium acetate with organic or inorganic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, and the like.

Suitable catalysts for catalytic reduction such as platinum catalysts of platinum plate, platinum sponge, platinum black, colloidal platinum, platinum oxide, platinum wire, etc.; palladium catalysts such as palladium sponge, palladium black, palladium oxide, palladium-carbon, colloidal palladium, palladium-barium sulfate, palladium-barium carbonate, and the like; nickel catalysts such as reduced nickel and Raney nickel (Raney nickel); reducing cobalt catalysts such as cobalt and Raney cobalt; reduced iron, raney iron and other iron catalysts; reducing copper catalysts commonly used, such as copper, Raney copper, Ullmann copper (Ullmann copper), and the like.

The reduction is usually carried out in a conventional solvent having no influence on the reaction, such as water, methanol, ethanol, propanol, and N, N-dimethylformamide, or a mixture thereof. Furthermore, when the above acids used for the chemical reduction are liquids, they can also be used as solvents.

Suitable solvents for the catalytic reduction are, in addition to the above-mentioned solvents, other common solvents such as diethyl ether, dioxane, tetrahydrofuran, etc., or mixtures thereof.

The reduction temperature is not particularly limited, and the reaction can be usually carried out under cooling or heating. The preparation method 3 comprises the following steps:

the object compound (I-4) or a salt thereof can be produced by oxidizing the compound (I-3) or a salt thereof.

In the case of obtaining the target compound (I-4) by oxidation, sodium chlorite, chromic anhydride, potassium permanganate and the like can be used as the oxidizing agent, and water, acetone and the like can be used as the solvent. The reaction temperature is not particularly limited, and the reaction can be usually carried out under cooling or heating. The preparation method 4 comprises the following steps:

the object compound (I-6) or a salt thereof can be produced by acylating the compound (I-5) or a salt thereof.

When the target compound (I-6) is obtained by acylation, the compound (I-5) having a terminal hydroxyl group may be reacted with an acylating agent. Examples of the acylating agent include lower alkanesulfonyl halides such as methanesulfonyl chloride, and lower alkanesulfonic anhydrides (e.g., methanesulfonic anhydride). The solvent may be dichloromethane, tetrahydrofuran, or the like, and the reaction is carried out in an ice water bath to room temperature. The preparation method 5:

The object compound (I-7) or a salt thereof can be produced by introducing an aryloxy group into the compound (I-6) or a salt thereof.

When the aryloxy group is introduced, the compound (I-6) having an acyloxy lower alkyl group at the terminal may be reacted with a hydroxyaryl group (e.g., phenol) in the presence of a base such as sodium hydroxide. The solvent may be N, N-dimethylformamide, tetrahydrofuran or the like, and the reaction is carried out in an ice water bath to room temperature. The preparation method 6 comprises the following steps:

the object compound (I-8) or a salt thereof can be produced by introducing a carboxyl protecting group into the compound (I-4) or a reactive derivative thereof.

The introduction of the carboxyl-protecting group can be carried out, for example, by reacting the compound (I-4) having a terminal carboxyl group and a reactive derivative thereof with an alkanol such as ethanol. The solvent may be N, N-dimethylformamide, dichloromethane or the like, and the reaction is carried out under ice-water bath to heating conditions.

Suitable reactive derivatives at the carboxyl group may include acid halides, acid anhydrides, activated amides, activated esters, and the like. Preferred examples of these reactive derivatives may be acyl chlorides; an acyl azide; mixed acid anhydrides formed with acids such as substituted phosphoric acids (e.g., dialkyl phosphoric acid, phenyl phosphoric acid, diphenyl phosphoric acid, benzhydryl phosphoric acid, halogenated phosphoric acids, etc.), dialkyl phosphorous acid, sulfurous acid, sulfuric acid, thiosulfuric acid, sulfonic acids (e.g., methanesulfonic acid, etc.), aliphatic carboxylic acids (e.g., acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, valeric acid, isovaleric acid, 2-ethylbutyric acid, trichloroacetic acid, etc.), or aromatic carboxylic acids (e.g., benzoic acid, etc.); a symmetric anhydride; an active amide with imidazole, 4-substituted imidazole, dimethylpyrazole, triazole or tetrazole; active esters (e.g. cyanomethyl, methoxymethyl, dimethyliminomethyl [ ] (CH₃)₂N⁺CH- ]ester, vinyl ester, propargyl ester, p-nitrophenyl ester, 2, 4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, methanesulfonylphenyl ester, phenylazophenyl ester, thiophenyl ester, p-nitrophenylthio ester, p-tolylthio ester, carboxymethylthio ester, pyranyl ester, pyridyl ester, piperidyl ester, 8-quinolylthio ester, etc.) or an ester with an N-hydroxy compound (e.g., N-dimethylhydroxylamine, 1-hydroxy-2-1H-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole, etc.), etc. These reactive derivatives can be arbitrarily selected depending on the kind of the compound used. The preparation method 7 comprises the following steps:

the object compound (I-9) or a salt thereof can be produced by introducing a carboxyl-protecting group into the compound (I-4) or a salt thereof.

When an alkylamine such as methylamine or ethylamine is reacted with the compound (I-4), the compound can be amidated. As the solvent used, for example, tetrahydrofuran, dichloromethane, N-dimethylformamide and the like can be used, and the reaction can be carried out under ice water bath to heating conditions. The preparation method 8 comprises the following steps:

the object (I-11) or a salt thereof can be produced by adding a nitrogen-containing heterocyclic group to the compound (I-10) or a salt thereof.

The reaction is preferably carried out in the presence of sodium tert-butyrate or a base such as the above-mentioned inorganic or organic base, and further preferably in the presence of a catalyst such as tris (dibenzylideneacetone) -dipalladium (O), (R) - (+) -BINAP [ 2, 2 '-bis (diphenylphosphino) -1, 1' -dinaphthyl ].

The reaction temperature is not particularly limited, and is preferably room temperature or heated, and the reaction may be carried out in the presence of a solvent such as toluene which does not adversely affect the reaction.

The above compounds can be purified by a common purification method for organic compounds, i.e., recrystallization, column chromatography, thin layer chromatography, high performance liquid chromatography, and the like, as necessary. The identification of the compound can be performed by NMR chromatography, mass spectrometry, IR chromatography, elemental analysis, melting point measurement, or the like.

The compounds of the invention may have more than 1 chiral center, and they may exist as enantiomers or diastereomers. Furthermore, certain compounds having an alkenyl group may exist as cis or trans isomers. For either case, the present invention includes mixtures thereof as well as various isomers.

The compounds of the invention and their salts can exist in the form of solvates, which are also included in the scope of the present invention. The solvate is preferably hydrate or ethanol.

In order to prove the usefulness of the objective compound (I), pharmacological data of the compound (I) are shown below. Test example 1

(hypoglycemic Effect on dd/db mice) test Compound A

3- (2, 4-Dichlorophenylmethyl) -2-methyl-5- (1-n-pentylsulfonylcarbamoyl) benzo [ b ] furan (the compound of example 30-1) animals were used

Female mice of 5 weeks old, C57BL/KsJ-dbm db +/db +, C57BL/KsJ-dbm + m/+ m (Jackson laboratory), were purchased and acclimated for 2-3 weeks for testing. Administration of drugs

The test material was mixed with a powdered feed (CE-2, Japanese clean) using a mortar. The mixing ratio was 0.1% for an administration amount of 100mg/kg, 0.03% for an administration amount of 30mg/kg, and 0.01% for an administration amount of 10 mg/kg. The feed was changed 2 times per week for each group, and the feed supply and feed residual were recorded and the difference between them was used to calculate the feed intake. Test schedule

Female db/db mice were divided into groups according to body weight, blood glucose level, and triglyceride concentration in plasma, and then administered with a drug-mixed feed for 14 days (test time was 8-10 weeks old). On day 7 and 14 in the morning, blood was taken from the orbital venous plexus using heparin-treated glass capillaries (Chase heparin capillary Tubes) and the plasma fraction was obtained by centrifugation. On day 0 and day 0 Blood glucose level, plasma triglyceride concentration, and plasma insulin concentration were measured on day 14, and blood glucose level and plasma triglyceride concentration were measured on day 7. In addition, body weights were measured on days 0, 7 and 14. After final bleeding, by CO₂The gas kills the mice. Measurement method

The blood glucose level was measured by the glucose oxidase method (glucose CII-test Waco, Waco, Wako pure chemical industries, Ltd.) using 10 to 15. mu.l of plasma. The triglyceride concentration in plasma was measured by the GPO-p-chlorophenol method (triglyceride G-test Waco) or the GPO-DAOS method (triglyceride E-test Waco) using 10 to 15. mu.l of plasma. The above measurement is performed quickly after blood sampling. Plasma insulin concentration was measured by the antibody method (Phadesef insulin RIA kit, Kabi pharmacia) using 20. mu.l of plasma (which can be stored at-20 ℃). Results

The difference between the blood glucose levels and the plasma triglyceride concentrations of the db/db mouse control group and the +/+ mice was defined as 100%, and the blood glucose level and the plasma triglyceride reduction rate (%) of the drug-administered group were determined. The results are shown in Table 1. [ TABLE 1 ]

Test compounds	Dosage (mg/kg)	Hypoglycemic Effect (%)
			Compound A	10	71

The compounds (I) of the present invention can be used in the form of pharmaceutical preparations for therapy. The pharmaceutical preparation is in the form of a mixture with a pharmaceutically acceptable organic or inorganic excipient suitable for oral, parenteral or topical (for topical use) solid, semi-solid or liquid preparations, containing any of the compounds as an active ingredient. As pharmaceutical preparations, for example, capsules, tablets, sugar-coated preparations, granules, suppositories, liquid preparations, lotions, suspensions, emulsions, ointments, gels and the like can be mentioned. These preparations may be supplemented with adjuvants, auxiliary substances, stabilizers, wetting or emulsifying agents, buffers, and other conventional additives as required.

The amount of compound (I) to be used varies depending on the age and symptoms of the patient, and the average one-time administration amount of compound (I) is about 0.1mg, 1mg, 10mg, 50mg, 100mg, 250mg, 500mg and 1000mg, which is effective for the treatment of the above-mentioned various diseases. It is generally preferred to administer from 0.1 mg/solid to about 1000 mg/solid per day. Examples

The present invention is further illustrated in detail by the following preparation examples and examples. Preparation example 1-13- (3, 4-Dichlorobenzoyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

The desired product was obtained from methyl 2-methylbenzo [ b ] thiophene-5-carboxylate and 3, 4-dichlorobenzoyl chloride in the same manner as in preparation example 16-2 described later.

¹H-NMR(CDCl₃)：2.48(3H，s)，3.89(3H，s)，7.52-7.68(2H，m)，7.79-8.04(3H，m)，8.23(1H，s)Mass(ESI)：m/e 377(M-H)^-Preparation example 1-23- (3, 4-Dichlorophenylmethyl) -2-methylbenzo [ b ]]Thiophene-5-carboxylic acid methyl ester

To 3- (3, 4-dichlorobenzoyl) -2-methylbenzo [ b ] under the condition of ice-water bath]To a solution of thiophene-5-carboxylic acid methyl ester (259mg) in tetrahydrofuran (2.6ml) -methanol (0.26ml) was added sodium borohydride (36mg), and the mixture was stirred for 10 minutes. Trifluoroacetic acid (15ml) was added to the other vessel, and sodium borohydride (255mg) was added little by little under ice-water bath conditions, followed by stirring. The reaction solution was further added thereto, and stirred at room temperature for 3 hours. The reaction mixture was concentrated, diluted with water under ice-water bath conditions, and neutralized with 15% aqueous sodium hydroxide solution. The product was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfateAnd (5) drying. The solvent was distilled off to leave the desired product (224mg) as a white powder.¹H-NMR(CDCl₃)：2.51(3H，s)，3.91(3H，s)，4.14(2H，s)，6.97(1H，dd，J＝8 and 2Hz)，7.20(1H，d，J＝2Hz)，7.31(1H，d，J＝8Hz)，7.82(1H，d，J＝8Hz)，7.93(1H，dd，J＝8 and 2Hz)，8.18(1H，d，J＝2Hz)Mass(ESI)：m/e 363(M-H)^-Preparation example 1-33- (3, 4-Dichlorophenylmethyl) -2-methylbenzo [ b ]]Thiophene-5-carboxylic acids

By the same method as in preparation examples 4 to 7 described later, from 3- (3, 4-dichlorobenzyl) -2-methylbenzo [ b ]]Thiophene-5-carboxylic acid methyl ester to obtain the target product.¹H-NMR(DMSO-d₆)：2.56(3H，s)，4.24(2H，s)，7.10(1H，d，J＝8Hz)，7.43(1H，s)，7.51(1H，d，J＝8Hz)，7.82(1H，d，J＝8Hz)，7.95(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz)Mass(ESI)：m/e 349(M-H)^-Preparation example 2-13- (2, 3-Dichlorobenzoyl) -2-methylbenzo [ b ]]Thiophene-5-carboxylic acid methyl ester

The objective compound was obtained in the same manner as in preparation example 1-1 using 2, 3-dichlorobenzoyl chloride. ¹H-NMR(CDCl₃)：2.40(3H，s)，3.90(3H，s)，7.31-7.41(2H，m)，7.58-7.69(1H，m)，7.81(1H，d，J＝8Hz)，8.01(1H，d，J＝8Hz)，8.59(1H，s)Mass(ESI)：m/e 377(M-H)^-Preparation example 2-23- (2, 3-Dichlorophenylmethyl) -2-methylbenzo [ b ]]Thiophene-5-carboxylic acid methyl ester

The desired product was obtained from the obtained methyl ester in the same manner as in production example 1-2.¹H-NMR(CDCl₃)：2.45(3H，s)，3.89(3H，s)，4.27(2H，s)，6.57(1H，d，J＝8Hz)，6.97(1H，t，J＝8Hz)，7.31(1H，d，J＝8Hz)，7.82(1H，d，J＝8Hz)，7.94(1H，d，J＝8Hz)，8.11(1H，s)Mass(ESI)：m/e 363(M-H)^-Preparation example 2-33- (2, 3-Dichlorophenylmethyl) -2-methylbenzo [ b]Thiophene-5-carboxylic acids

The desired product was obtained from the obtained methyl ester in the same manner as in production examples 1 to 3.¹H-NMR(DMSO-d₆)：2.50(3H，s)，4.32(2H，s)，6.71(1H，d，J＝8Hz)，7.19(1H，t，J＝8Hz)，7.51(1H，d，J＝8Hz)，7.83(1H，d，J＝8Hz)，8.01(1H，s)，8.02(1H，d，J＝8Hz)Mass(ESI)：m/e 349(M-H)^-Preparation example 3-13- (2, 5-Dichlorobenzoyl) -2-methylbenzo [ b ]]Thiophene-5-carboxylic acid methyl ester

The objective compound was obtained in the same manner as in preparation example 1-1 using 2, 5-dichlorobenzoyl chloride.¹H-NMR(CDCl₃)：2.42(3H，s)，3.90(3H，s)，7.35-7.51(3H，m)，7.81(1H，d，J＝8Hz)，8.01(1H，d，J＝8Hz)，8.06(1H，s)Mass(ESI)：m/e 377(M-H)^-Preparation example 3-23- (2, 5-Dichlorophenylmethyl) -2-methylbenzo [ b]Thiophene-5-carboxylic acid methyl ester

The desired product was obtained from the obtained methyl ester in the same manner as in production example 1-2.¹H-NMR(CDCl₃)：2.48(3H，s)，3.90(3H，s)，4.21(2H，s)，6.64(1H，s)，7.11(1H，d，J＝8Hz)，7.34(1H，d，J＝8Hz)，7.83(1H，d，J＝8Hz)，7.95(1H，d，J＝8Hz)，8.13(1H，s)Mass(ESI)：m/e 363(M-H)^-Preparation example 3-33- (2, 5-Dichlorophenylmethyl) -2-methylbenzo [ b]Thiophene-5-carboxylic acids

The desired product was obtained from the methyl ester obtained in the same manner as in production examples 1 to 3.¹H-NMR(DMSO-d₆)：2.52(3H，s)，4.28(2H，s)，6.75(1H，d，J＝2Hz)，7.33(1H，dd，J＝8 and 2Hz)，7.55(1H，d，J＝8Hz)，7.84(1H，d，J＝8Hz)，7.89-8.11(2H，m)Mass(ESI)：m/e 349(M-H)^-Preparation example 4-1N-Aminoisonicotinic acid Ethyl ester 2, 4-dinitrophenolate

Ethyl isonicotinate (10.0g) was dissolved in tetrahydrofuran (100ml), and 0- (2, 4-dinitrophenyl) hydroxylamine (11.9g) was added thereto at room temperature, followed by heating and refluxing for 2 hours. The solvent was distilled off under reduced pressure, and the residue was washed with diethyl ether and ethyl acetate to give the desired product (10.5g) as a brown powder. ¹H-NMR(DMSO-d₆): 1.36(3H, t, J ═ 6Hz), 4.40(2H, q, J ═ 6Hz), 6.32(1H, d, J ═ 9Hz), 7.78(1H, dd, J ═ 9,2Hz), 8.34(1H, d, J ═ 8Hz), 8.59(1H, d, J ═ 2Hz), 8.84(1H, d, J ═ 8Hz)Preparation 4-22-methylpyrazolo [1, 5-a ]]Pyridine-3, 5-dicarboxylic acid diethyl ester

Ethyl N-aminoisonicotinate 2, 4-dinitrophenolate (10.2g) was suspended in ethanol (147ml), and potassium carbonate (3.77g) was added thereto, followed by stirring at room temperature for 30 minutes. Ethylacetoacetate (3.69ml) was added to the mixture, which was then stirred at 60 ℃ for 5 hours. After insoluble matter was removed by filtration, the filtrate was concentrated under reduced pressure and dried to solidify, and the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate: 7/1) to give the desired product (2.70g) as a brown solid.¹H-NMR(CDCl₃): 1.42(3H, t, J ═ 6Hz), 1.46(3H, t, J ═ 6Hz), 2.70(3H, s), 4.36-4.50(4H, m), 7.46(1H, d, J ═ 8Hz), 7.78(1H, dd, J ═ 9,2Hz), 8.43(1H, d, J ═ 8Hz), 8.78(1H, s), preparation 4-32-methylpyrazolo [1, 5-a ]]Pyridine-3, 5-dicarboxylic acids

2-methylpyrazolo [1, 5-a ]]After a mixture of diethyl pyridine-3, 5-dicarboxylate (100mg), 50% aqueous sodium hydroxide solution (160mg), water (0.5ml) and ethanol (1.0ml) was heated under reflux for 30 minutes, the pH of the liquid was adjusted to 4 under ice-water bath conditions, and the mixture was stirred at the same temperature for 30 minutes. The precipitate was filtered and washed with water to give the desired product as a pale brown powder (50 mg). ¹H-NMR(DMSO-d₆): 2.55(3H, s), 7.43(1H, d, J ═ 8Hz), 8.46(1H, s), 8.56(1H, d, J ═ 8Hz)]Pyridine-5-carboxylic acid

A mixture of 2-methylpyrazolo [1, 5-a ] pyridine-3, 5-dicarboxylic acid (1.39g) and polyphosphoric acid (13.9g) was heated and stirred at 150 ℃ for 2 hours, and then ice (14g) was added under ice-water bath conditions, followed by shaking to obtain a uniform solution. The liquid was adjusted to pH4 at the same temperature, diluted with methylene chloride/methanol (4: 1) and water, and the precipitate was filtered to give the desired product (610mg) as a pale brown powder. The organic layer was separated from the mother liquor and the aqueous layer was extracted with dichloromethane/methanol (4: 1). The organic layers were combined, dried over magnesium sulfate, and then concentrated and dried under reduced pressure to solidify. The residue was washed with diethyl ether to give secondary crystals (200mg) as a pale brown powder.

¹H-NMR(DMSO-d₆): 2.42(3H, s), 6.67(1H, s), 7.18(1H, d, J ═ 8Hz), 8.21(1H, s), 8.62(1H, d, J ═ 8Hz)]Pyridine-5-carboxylic acid ethyl ester

2-methylpyrazolo [1, 5-a ]]Pyridine-5-carboxylic acid (723mg) was dissolved in 10% sulfuric acid/ethanol (20ml), and the mixture was refluxed for 2.5 hours. The reaction solution was neutralized in an ice-water bath, extracted with ethyl acetate, dried over magnesium sulfate, and concentrated and dried under reduced pressure to solidify. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 4: 1) to give the desired product (707mg) as a pale brown powder. ¹H-NMR(CDCl₃): 1.41(3H, t, J ═ 7Hz), 2.52(3H, s), 4.40(2H, q, J ═ 7Hz), 6.49(1H, s), 7.25(1H, d, J ═ 8Hz), 8.19(1H, s), 8.40(1H, d, J ═ 8Hz), preparation 4-63- (2, 4-dichlorobenzyl) -2-methylpyrazolo [1, 5-a ] of example 4]Pyridine-5-carboxylic acid ethyl ester

To a solution of trifluoroacetic acid (558mg), triethylsilane (1.14g) and dried dichloromethane (2.0ml) was added 2-methylpyrazolo [1, 5-a ]]Pyridine-5-carboxylic acid ethyl ester (200mg) and 2, 4-dichlorobenzaldehyde (189mg) were stirred at room temperature for 3 days. 2, 4-Dichlorobenzaldehyde (189mg) was added to the reaction mixture and stirred at room temperature for 1 day, and this operation was repeated 3 times. The reaction mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium hydrogencarbonate, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over magnesium sulfate, concentrated and dried under reduced pressure to solidify. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 9: 1) and further washed with isopropyl ether to give the desired product (233mg) as a white powder.¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 7Hz), 2.38(3H, s), 4.12(2H, s), 4.38(2H, q, J ═ 7Hz), 6.84(1H, d, J ═ 8Hz), 7.10(1H, d, J ═ 8Hz), 7.27(1H, d, J ═ 8Hz), 7.42(1H, s), 8.00(1H, s), 8.40(1H, d, J ═ 8Hz), preparation 4-73- (2, 4-dichlorobenzyl) -2-methylpyrazolo [1, 5-a ], ]Pyridine-5-carboxylic acid

3- (2, 4-dichlorobenzyl) -2-methylpyrazolo [1, 5-a]Pyridine-After a mixture of ethyl 5-carboxylate (230mg), 1N aqueous sodium hydroxide solution (2.0ml) and ethanol (2.3ml) was heated under reflux for 25 minutes, the liquid was adjusted to pH4 with 1N hydrochloric acid under ice-water bath conditions. The resulting precipitate was filtered and washed with water to give the desired product (208mg) as a white powder.¹H-NMR(DMSO-d₆): 2.30(3H, s), 4.19(2H, s), 7.10(1H, d, J ═ 8Hz), 7.16(1H, d, J ═ 8Hz), 7.34(1H, d, J ═ 8Hz), 7.62(1H, s), 8.06(1H, s), 8.62(1H, d, J ═ 8Hz)

Diisopropylamine (16.2g) was dissolved in tetrahydrofuran (133ml), and 1.6N N-butyllithium (100ml) was added dropwise under ice-water bath conditions. After stirring at the same temperature for 10 minutes, a solution of 2, 4-dichloroacetophenone (25.2g) in tetrahydrofuran (133ml) was added dropwise while cooling in a dry ice-acetone bath, and hexamethylphosphoramide (26.7ml) was further added slowly. After stirring at the same temperature for 5 minutes, chlorotrimethylsilane (20.3ml) was added dropwise thereto, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was separated with ice-cold n-hexane and ice-water, the organic layer was washed with ice-water 2 times and saturated brine 1 time, and then dried over sodium sulfate, concentrated and dried under reduced pressure to solidify the product, to obtain a crude product (37.5g) as a pale yellow oil. Preparation example 5-21- (2, 4-dichlorophenyl) -3-hydroxy-3-methylbutanone

Acetone (10ml) was added dropwise to a dichloromethane (160ml) solution of titanium tetrachloride (17.8ml) with cooling in a dry ice-acetone bath, and after 1 minute, a dichloromethane (160ml) solution of a crude product (37.5g) of 1- (2, 4-dichlorophenyl) -1-trimethylsiloxyethylene was added, and after stirring for 1 night in a dry ice-acetone bath, the mixture was further stirred at room temperature for 3 hours. The reaction solution was washed with water, and the aqueous layer was extracted 1 time with dichloromethane. The organic layers were combined, washed with a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, dried over magnesium sulfate, concentrated and dried under reduced pressure to solidify, thereby obtaining a brown oily residue. This was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate: 9/1-4/1) to give the desired product (16.2g) as a pale yellow oil.¹H-NMR(CDCl₃)：1.34(6H，s)，3.13(2H，s)，7.33(1H，d, J ═ 8Hz), 7.44(1H, d, J ═ 8Hz), 7.47(1H, s.) preparation of 5-31- (2, 4-dichlorophenyl) -3-methyl-3-trifluoroacetyloxybutanone

Trifluoroacetic anhydride (13.9ml) was added to a dichloromethane (160ml) solution of 1- (2, 4-dichlorophenyl) -3-hydroxy-3-methylbutanone (16.16g) and triethylamine (27.4ml) under ice-water bath conditions, followed by stirring at the same temperature for 10 minutes and at room temperature for 1 hour. The reaction mixture was washed with water and a saturated aqueous solution of sodium hydrogencarbonate, dried over sodium sulfate, and concentrated and dried under reduced pressure to solidify the product, to obtain a crude product (19.9g) as a brown oily desired product. Preparation example 5-41- (2, 4-dichlorophenyl) -3-methyl-2-butenone

To a solution of crude 1- (2, 4-dichlorophenyl) -3-methyl-3-trifluoroacetyloxybutanone (19.9g) in toluene (100ml) was added 1, 8-diazabicyclo [5, 4, 0 ]]Undec-7-ene (4.0ml), stirred at room temperature for 30 minutes. The reaction mixture was washed with ice water, 1N hydrochloric acid, saturated brine, saturated aqueous solution of sodium hydrogencarbonate and saturated brine in this order, dried over magnesium sulfate, and concentrated under reduced pressure to dry and solidify. The residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate 49/1) to give the desired product (12.5g) as a pale brown oil.¹H-NMR(CDCl₃): 2.00(3H, s), 2.24(3H, s), 6.43(1H, s), 7.29(1H, d, J ═ 8Hz), 7.39-7.46 (2H.) preparation 5-5(E) 4-bromo-1- (2, 4-dichlorophenyl) -3-methyl-2-butenone

To a solution of 1- (2, 4-dichlorophenyl) -3-methyl-2-butenone (9.30g) in carbon tetrachloride (93ml) were added N-bromosuccinimide (7.95g) and benzoyl peroxide (983mg), and the mixture was refluxed for 1 hour. After the reaction solution was cooled with ice, the precipitate was filtered, and the filtrate and the washing solution were combined, washed 3 times with a saturated aqueous solution of sodium hydrogencarbonate and 1 time with saturated brine. The organic layer was dried over magnesium sulfate, concentrated and dried under reduced pressure to solidify the organic layer, whereby the crude product (14.6g) was obtained as a black oily substance. Preparation example 5-6(E)1- (2, 4-dichlorophenyl) -4- (4-ethoxycarbonylpyridyl) -3-methyl-2-butenone

The crude product (14.6g) of (E) 4-bromo-1- (2, 4-dichlorophenyl) -3-methyl-2-butenone was dissolved in acetone (140ml), and ethyl isonicotinate (12.1ml) was added to the solution, followed by refluxing under heating for 6 hours. The reaction mixture was concentrated under reduced pressure, and dried and solidified to obtain a crude product (22.0g) of the objective product as a brown solid. Preparation example 5-71- (2, 4-Dichlorobenzoyl) -2-methylindolizine-7-carboxylic acid ethyl ester

The crude product (22.0g) of (E)1- (2, 4-dichlorophenyl) -4- (4-ethoxycarbonylpyridyl) -3-methyl-2-butenone was dissolved in ethanol (146ml), and potassium carbonate (5.61g) was added to the solution, followed by refluxing under heating for 12 hours. The reaction mixture was separated with ethyl acetate and saturated brine, and the organic layer was dried over magnesium sulfate, concentrated and dried under reduced pressure to solidify the mixture to obtain a brown solid. The residue was pulverized in diethyl ether to give the desired product (3.54g) as a yellow powder.¹H-NME(CDCl₃): 1.38(3H, t, J ═ 6Hz), 2.16(3H, s), 4.35(2H, q, J ═ 6Hz), 7.22(1H, s), 7.30-7.42(3H), 7.52(1H, s), 7.97(1H, d, J ═ 8Hz), 8.36(1H, s), preparation of ethyl 5-81- (2, 4-dichlorobenzyl) -2-methylindolizine-7-carboxylate

Ethyl 1- (2, 4-dichlorobenzoyl) -2-methylindolizine-7-carboxylate (3.17g) was dissolved in tetrahydrofuran (32ml), and 10M borane-dimethylsulfide complex (9.5ml) was added dropwise under ice-water bath conditions. After stirring at room temperature for 3.5 hours, the reaction mixture was neutralized and separated with ethyl acetate and water. The organic layer was washed with water 3 times, then with saturated brine, dried over magnesium sulfate, and concentrated and dried under reduced pressure to solidify. The residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate 19/1) to give the desired product (1.81g) as a pale yellow oil. ¹H-NMR(CDCl₃): 1.38(3H, t, J ═ 6Hz), 2.13(3H, s), 4.16(2H, s), 4.33(2H, q, J ═ 6Hz), 6.71(1H, d, J ═ 8Hz), 6.99(1H, d, J ═ 8Hz), 7.03(1H, dd, J ═ 8,2Hz), 7.29(1H, s), 7.40(1H, s), 7.80(1H, d, J ═ 8Hz), 7.98(1H, s), preparation 5-91- (2, 4-dichlorobenzyl) -2-methylindolizine-7-carboxylic acid

From 1- (2, 4-dichlorobenzyl) -2-methyl group, the same procedure was followed as in preparation examples 4-7Ethyl indolizine-7-carboxylate (1.81g) gave the desired product (1.63g) as a yellow powder.¹H-NMR(DMSO-d₆): preparation of 6-1(E) -4-methyl-2- (4-phenylphenyl) vinylpyridine from example 10(3H, s), 4.17(2H, s), 6.84-6.91(2H), 7.28(1H, d, J ═ 8Hz), 7.60(2H, s), 7.93(1H, s), 8.19(1H, d, J ═ 8Hz)

A mixture of 4-phenylbenzaldehyde (6.45g), 2, 4-lutidine (7.59g) and acetic anhydride (10ml) was heated at a bath temperature of 150 ℃ for 12 hours, and then heated under reflux for 12 hours. The reaction mixture was concentrated and dried under reduced pressure to solidify it. The residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate: 9/1-5/1) to obtain the desired product (4.35g) as a yellow solid.¹H-NMR(CDCl₃): 2.38(3H, s), 6.98(1H, d, J ═ 5Hz), 7.12 to 7.28(2H), 7.34(1H, t, J ═ 8Hz), 7.44(2H, t, J ═ 8Hz), 7.56 to 7.71(7H), 8.47(1H, d, J ═ 5Hz)

A mixture of (E) -4-methyl-2- (4-phenylphenyl) vinylpyridine (4.24g), selenium dioxide (2.08g) and pyridine (43ml) was heated under reflux for 24 hours. The reaction mixture was concentrated and dried under reduced pressure to solidify, and the residue was extracted with chloroform/methanol/aqueous ammonia (65: 25: 4). The dried extract was concentrated under reduced pressure to solidify it, and the residue was pulverized in ethyl acetate to give the desired product (3.81g) as a brown powder.¹H-NMR(DMSO-d₆): 7.32-7.53(4H), 7.63(1H, d, J ═ 5Hz), 7.70-7.84(8H), 7.96(1H, s), 8.66(1H, d, J ═ 5Hz), preparation 6-3(E) -2- (4-phenylphenyl) vinylpyridine-4-carboxylic acid ethyl ester

A mixture of (E) -2- (4-phenylphenyl) vinylpyridine-4-carboxylic acid (3.60g) and concentrated sulfuric acid/ethanol (9: 1) was heated under reflux for 2 hours, and then neutralized under ice-water bath conditions. The reaction mixture was quenched with dichloromethane and water, and the aqueous layer was extracted 1 time with dichloromethane. The organic layers were combined, dried over magnesium sulfate, concentrated and dried under reduced pressure to solidify. Purifying the residue by silica gel column chromatography (eluting solvent: hexane/ethyl acetate 9/1-4/1) to obtain the desired product (b)3.14g)。¹H-NMR(CDCl₃): 1.43(3H, t, J ═ 6Hz), 4.45(2H, q, J ═ 6Hz), 7.22 to 7.50(4H), 7.60 to 7.79(8H), 7.97(1H, s), 8.74(1H, d, J ═ 5Hz), preparation 6-42- (4-phenylphenyl) ethylpyridine-4-carboxylic acid ethyl ester

A mixture of ethyl (E) -2- (4-phenylphenyl) vinylpyridine-4-carboxylate (1.84g), 10% palladium on activated carbon (184mg), dioxane (18ml) and ethanol (9.0ml) was stirred at 40 ℃ for 5 hours under a hydrogen pressure of 5 atm. Dioxane (9.0ml) and ethanol (9.0ml) were added to the mixture, and after stirring at 50 ℃ for 3 hours under a hydrogen pressure of 5 atm, 10% palladium on activated carbon (184mg) was added, and further stirring was carried out under the same conditions for 3 hours. The reaction mixture was filtered through celite, washing with chloroform/methanol (4: 1). The filtrate and the washing liquid were combined, concentrated and dried under reduced pressure to solidify the mixture, whereby the crude product (1.97g) of the objective product was obtained as a pale yellow solid.¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 6Hz), 3.12(2H, m), 3.22(2H.m), 4.40(2H, q, J ═ 6Hz), 7.22 to 7.36(3H), 7.43(2H, t, J ═ 8Hz), 7.52(2H, d, J ═ 8Hz), 7.58(2H, d, J ═ 8Hz), 7.67 to 7.72(2H), 8.72(1H, d, J ═ 5Hz), preparation 6-52-methyl-1- (4-phenylbenzyl) indolizine-7-carboxylic acid ethyl ester

A crude product of ethyl 2- (4-phenylphenyl) ethylpyridine-4-carboxylate (1.62g) and bromoacetone (803mg) were dissolved in acetone (32ml), and the mixture was refluxed for 24 hours and then concentrated and dried under reduced pressure to solidify the mixture. The residue was dissolved in ethanol (16ml), and sodium hydrogencarbonate was added to the solution to reflux under heating for 12 hours. After the reaction mixture was diluted with ethyl acetate, the mixture was washed with water, and the organic layer was dried over magnesium sulfate, concentrated and dried under reduced pressure to solidify the mixture. The residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate ═ 19/1) to give the desired product (383mg) as a yellow-green solid, and the unreacted starting material ethyl 2- (4-phenylphenyl) ethylpyridine-4-carboxylate (1.04g) was recovered. ¹H-NMR(CDCl₃)：1.38(3H，t，J＝6Hz)，2.21(3H，s)，4.19(2H，s)，4.35(2H，q，J＝6Hz)，6.98(1H，d，J＝8Hz)，7.18-7.36(4H)，7.40(2H，t，J＝8Hz)，7.48(2H，d，J＝8Hz) 7.56(2H, d, J ═ 8Hz), 7.78(1H, d, J ═ 8Hz), 8.12(1H, s), preparation 6-62-methyl-1- (4-phenylbenzyl) indolizine-7-carboxylic acid

The desired product (612mg) was obtained as a yellow powder from ethyl 2-methyl-1- (4-phenylbenzyl) -indolizine-7-carboxylate (710mg) according to the same manner as in preparation examples 4-7.¹H-NMR(DMSO-d₆): 2.20(3H, s), 4.16(2H, s), 6.86(1H, d, J ═ 8Hz), 7.22(2H, d, J ═ 8Hz), 7.33(1H, t, J ═ 8Hz), 7.43(2H, t, J ═ 8Hz), 7.52-7.64(5H), 8.06(1H, s), 8.17(1H, d, J ═ 8Hz)

A mixture of quinoline-6-carboxylic acid (4.00g) and thionyl chloride (10.1ml) was stirred at room temperature for 3 hours, then concentrated under reduced pressure and dried to solidify. After methylene chloride (60ml) and triethylamine (16ml) were added to the residue, 2-amino-2-methylpropanol (4.12g) was added thereto while stirring in a water bath, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted 2 times with dichloromethane. The organic layers were combined, dried over anhydrous magnesium sulfate, concentrated and dried under reduced pressure to solidify the mixture, to give a pale brown solid (5.55 g). Thionyl chloride (16.8ml) was added thereto under nitrogen ice-water bath conditions with stirring, and stirred at room temperature for 3 hours. After concentrating and drying under reduced pressure to solidify, water and a 1N aqueous solution of sodium hydroxide were added to adjust the mixture to be alkaline, and the mixture was extracted with ethyl acetate 3 times. After drying over anhydrous magnesium sulfate, the mixture was concentrated and dried under reduced pressure to solidify the mixture, and the residue was purified by silica gel column chromatography (elution solvent: ethyl acetate) to obtain the desired product (3.26g) as a pale brown solid. ¹H-NMR(CDCl₃): 1.43(6H, s), 4.20(2H, s), 7.45(1H, dd, J ═ 4Hz, 8Hz), 8.11(1H, d, J ═ 8Hz), 8.21(1H, d, J ═ 8Hz), 8.26(1H, d, J ═ 8Hz), 8.43(1H, s), 8.97(1H, m), preparation 7-21-ethoxycarbonyl-6- (4, 5-dihydro-4, 4-dimethyloxazol-2-yl) -2-dimethoxyphosphoryl-1, 2-dihydroquinoline

A mixture of 6- (4, 5-dihydro-4, 4-dimethyloxazol-2-yl) quinoline (543mg) and ethyl chloroformate (0.275ml) was stirred at room temperatureAfter stirring for 3 hours, trimethyl phosphate (0.340ml) was added in an ice-water bath and stirred at room temperature for 15 hours. The reaction mixture was concentrated and dried under reduced pressure to solidify, and the residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate, ethyl acetate/methanol: 20/1) to give the desired product (974mg) as a pale yellow oil.¹H-NMR(CDCl₃): 1.33(3H, t, J ═ 7Hz), 1.39(6H, s), 3.52(3H, d, J ═ 10Hz), 3.64(3H, d, J ═ 10Hz), 4.12(2H, s), 4.26 to 4.38(2H, br), 5.61 to 5.75(1H, br), 6.06 to 6.14(1H, m), 6.62(1H, m), 7.68(1H, s), 7.78(1H, dd, J ═ 4Hz, 8Hz), preparation of example 7-31-ethoxycarbonyl-6- (4, 5-dihydro-4, 4-dimethyloxazol-2-yl) -2-dimethoxyphosphoryl-4- (4-phenylbenzyl) -1, 2-dihydroquinoline

1-ethoxycarbonyl-6- (4, 5-dihydro-4, 4-dimethyloxazol-2-yl) -2-dimethoxyphosphoryl-1, 2-dihydroquinoline (934mg) was dissolved in THF (10ml), and a 1.6M n-butyllithium hexane solution (1.8ml) was added under cooling with dry ice-acetone, followed by stirring at the same temperature for 1 hour. 4- (iodomethyl) biphenyl (740mg, 2.52mmol) was added under dry ice acetone cooling, stirred at-20 ℃ for 1 hour, further stirred at 0 ℃ for 1 hour, added with water, and stirred at room temperature for 0.5 hour. The extract was extracted with ethyl acetate 3 times, dried over anhydrous magnesium sulfate, concentrated and dried under reduced pressure to solidify the extract, and the residue was purified by silica gel column chromatography (elution solvent: ethyl acetate, ethyl acetate/methanol: 20/1) to give the desired product (738mg) as a yellow powder.¹H-NMR(CDCl₃): 1.32(3H, t, J ═ 7Hz), 1.38(6H, s), 3.49(3H, d, J ═ 10Hz), 3.61(3H, d, J ═ 10Hz), 3.99(2H, br), 4.10(2H, m), 4.30(2H, m), 5.54-5.74(2H, br), 7.29-7.60(10H, m), 7.84(1H, m), 7.91(1H, s), MS (m/z)575. preparation 7-46- (4, 5-dihydro-4, 4-dimethyloxazol-2-yl) -4- (4-phenylbenzyl) quinoline

A mixture of 1-ethoxycarbonyl-6- (4, 5-dihydro-4, 4-dimethyloxazol-2-yl) -2-dimethoxyphosphoryl-4- (4-phenylphenylmethyl) -1, 2-dihydroquinoline (738mg), ethanol (20ml) and 1N aqueous sodium hydroxide solution (4ml) was heated under reflux for 2 hours. Concentrating the reaction mixture under reduced pressure The mixture was added with water and extracted 2 times with ethyl acetate. The organic layers were combined, washed with saturated brine 1 time, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and dried to solidify. The residue was purified by silica gel column chromatography (elution solvent: ethyl acetate) to give the desired product (140mg) as a white solid.¹H-NMR(CDCl₃): 1.42(6H, s), 4.18(2H, s), 4.54(2H, s), 7.18(1H, br), 7.27-7.46(5H, m), 7.52-7.60(4H, m), 8.16(1H, d, J ═ 8Hz), 8.29(1H, d, J ═ 8Hz), 8.73(1H, br), 8.83(1H, d, J ═ 7Hz)

A mixture of 6- (4, 5-dihydro-4, 4-dimethyloxazol-2-yl) -4- (4-phenylbenzyl) quinoline (132mg), ethanol (1ml) and 3N hydrochloric acid (3ml) was heated under reflux for 2 hours, followed by addition of 6N hydrochloric acid (3ml) and heating under reflux for 4 hours. After adding an aqueous sodium hydroxide solution to make the mixture alkaline, the mixture was washed with chloroform 1 time. The aqueous phase was adjusted to pH4 with 1N hydrochloric acid, and the resulting precipitate was filtered and washed with water to give the desired product (87mg) as a white powder.¹H-NMR(DMSO-d₆): 4.61(2H, s), 7.30-7.50(6H, m), 7.57-7.68(4H, m), 8.12(1H, d, J ═ 8Hz), 8.21(1H, d, J ═ 8Hz), 8.83(1H, s), 8.94(1H, d, J ═ 4Hz), preparation 8-12, 3-diamino-6-chloropyridine

The desired product (8.3g) was obtained as a reddish brown solid from 2-amino-6-chloro-3-nitropyridine (10.2g) in the same manner as in preparation example 9-2 described below.¹H-NMR(DMSO-d₆): 4.77(2H, br s), 5.79(2H, br s), 6.34(1H, d, J ═ 8Hz), 6.69(1H, d, J ═ 8Hz). M/z 142(M-1) preparation 8-25-chloro-2-methyl-1H-imidazo [ 4, 5-b ] pyridine

The objective product (6.64g) was obtained as pale brown crystals from 2, 3-diamino-6-chloropyridine (8.1g) in the same manner as in production example 9-3 described below.¹H-NMR(DMSO-d₆): 2.52(3H, s), 7.22(1H, d, J ═ 8Hz), 7.91(1H, d, J ═ 8Hz). M/z 166(M-1) mp 254-

According to the following relationThe same procedures used in preparation example 9-1 were repeated except for using 5-chloro-2-methyl-1H-imidazo [ 4, 5-b ] pyridine (6.54g) to give the desired product as pale purple crystals (7.54 g).¹H-NMR(DMSO-d₆): 2.51(3H, s), 7.32(1H, d, J ═ 8Hz), 7.83(1H, d, J ═ 8Hz). M/z 210(M-1) mp 239-

Copper (I) cyanide (2.04g) was added to a solution of 5-bromo-2-methyl-1H-imidazo [ 4, 5-b ] pyridine (1.92g) in N, N-dimethylformamide (48ml), and the mixture was stirred at 150 ℃ for 9 hours. The solvent was distilled off under reduced pressure, and water (45ml) and ethylenediamine (2.7g) were added to the residue to heat at 70 ℃ for 15 minutes. The solution was concentrated under reduced pressure and purified through a short column of silica gel to obtain the objective product (927mg) as a brown powder. Further, the extract was purified by silica gel column chromatography (dichloromethane/methanol: 10/1) to obtain a pure substance. ¹H-NMR(DMSO-d₆)：2.58(3H，s)，7.76(1H，d，J＝8Hz)，8.05(1H，d，J＝8Hz).Mass(ESI)：m/e 157(M-H)^-Preparation example 9-12 amino-6-bromo-3-nitropyridine

To 2-amino-6-chloro-3-nitropyridine (1.0g) was added 30% acetic acid hydrogen bromide solution (10ml) at room temperature, and the mixture was heated to 100 ℃. After 24 hours, a further 30% acetic acid hydrogen bromide solution (5ml) was added. After 48 hours the reaction was cooled and concentrated. The residue was neutralized with 28% aqueous ammonia, and extracted with ethyl acetate 3 times. Dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was crystallized from isopropyl ether to give the desired product (1.14g) as yellow crystals.¹H-NMR(DMSO-d₆): 6.90(1H, d, J ═ 8Hz), 8.25(1H, d, J ═ 8Hz), masss (esi): m/z 217(M-1) preparation 9-22, 3-diamino-6-bromopyridine

To a suspension of 2-amino-6-bromo-3-nitropyridine (21.8g) in ethanol (220ml) -water (22ml) was added iron powder (39.0g) at room temperature. Concentrated hydrochloric acid (0.8ml) was added and the reaction was started by slowly heating while stirring. After heating and refluxing for 2 hours, insoluble matter was removed by filtration while it was hot. The solvent was distilled off under reduced pressure, and water (200ml) and activated carbon were added to the remaining solid, followed by heating. Filtering to remove insoluble substances, and distilling under reduced pressureThe filtrate was freed of water to give the desired product as a greenish brown powder (9.00 g). Ethanol (100ml) -water (100ml) was added to the solid remaining from the above operation, and the insoluble matter was removed by heating, dissolution and filtration. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 1/3) to obtain the desired product (8.25g) as a black powder. ¹H-NMR(DMSO-d₆)：4.78(2H，br s)，5.80(2H，br s)，6.47(1H，d，J＝8Hz)，6.61(1H，d，J＝8Hz).Mass(ESI)：m/e 188，190(M+H)⁺Preparation example 9-35-bromo-2-methyl-1H-imidazo [ 4, 5-b ] pyridine

2, 3-diamino-6-bromopyridine (8.16g) and triethyl orthoacetate (12.0ml) were mixed in acetic acid (41ml), and the mixture was refluxed for 29 hours. The reaction mixture was cooled and the solvent was distilled off under reduced pressure to obtain a crude product (10 g). It was dissolved in a sufficient amount of methylene chloride, and anhydrous potassium carbonate and activated carbon were added and stirred at room temperature. Insoluble matter was removed by filtration, and the solvent was distilled off to obtain the objective product (7.59g) as a pale yellow powder.¹H-NMR(DMSO-d₆)：2.51(3H，s)，7.31(1H，d，J＝8Hz)，7.82(1H，d，J＝8Hz).Mass(ESI)：m/e 212，214(M+H)⁺Preparation example 10-13- (2, 4-Dichlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile and 1- (2, 4-Dichlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

According to the same manner as in preparation example 14-2 below, from 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (200mg) were obtained light brown crystalline 2 isomers of 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (138mg) and 1- (2, 4-dichlorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (67mg), respectively.

3- (2, 4-Dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

¹H-NMR(CDCl₃)：2.60(3H，s)，5.55(2H，s)，6.64(1H，d，J＝8Hz)，7.14(1H，dd，J＝8,2Hz)，7.48(1H，br s)，7.65(1H，d，J＝8Hz)，8.09(1H，br d，J＝8Hz).MASS(ESI)：m/z 317(M+1)，mp 180-182℃

1- (2, 4-Dichlorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

¹H-NMR(CDCl₃): 2.67(3H, br s), 5.42(2H, s), 6.46(1H, d, J ═ 8Hz), 7.18(1H, d, J ═ 8Hz), 7.49-7.60(3H, m), mass (esi): m/z 317(M +1) preparation 10-23- (2, 4-Dichlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

To a suspension of 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (113mg) in ethanol (0.6ml) was added a 30% aqueous sodium hydroxide solution (0.3ml), and the mixture was refluxed for 12 hours. After 12 hours, a 30% aqueous solution (0.5ml) of sodium hydroxide was further added thereto, and the mixture was refluxed for 3 hours. The reaction solution was cooled, adjusted to pH1 with 6N hydrochloric acid, stirred for 1 hour, and adjusted to pH4 with a saturated aqueous solution of sodium hydrogencarbonate. The precipitated crystals were filtered to give the desired product (144mg) as colorless crystals.¹H-NMR(DMSO-d₆): 2.51(3H, s), 5.60(2H, s), 6.60(1H, d, J ═ 8Hz), 7.31(1H, br d, J ═ 8Hz), 7.76(1H, br s), 8.00(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), mas (esi): m/z 334(M-1) mp > 260 ℃ preparation of 11-12-chloro-4-phenylbenzyl alcohol

4-bromo-2-chlorobenzyl alcohol (1.05g), phenyltributyltin (1.74g), and tetrakis (triphenylphosphine) palladium (O) (110mg) were added to a suspension of lithium chloride (482mg) in anhydrous 1, 4-dioxane (12ml) under a nitrogen stream, and the mixture was refluxed. After 5 hours, the reaction was cooled, water was added, and extraction was performed with ethyl acetate. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and a saturated brine, and dried over anhydrous magnesium sulfate. The filtrate was concentrated, and the residue was subjected to flash silica gel column chromatography (silica gel 50ml), which was eluted with hexane-ethyl acetate ═ 2-1 and then washed with hexane to give the desired product (220mg) as colorless crystals. ¹H-NMR(CDCl₃): 4.72(2H, s), 7.32-7.61(8H, m). mp 69-70 deg.C preparation of 11-22-chloro-4-phenylbenzyl alcohol

To a suspension of tetrakis (triphenylphosphine) palladium (O) (16mg) in toluene (1ml) was added 4-bromo-2-chlorobenzyl alcohol (100mg) at room temperature, and the mixture was stirred. After 10 minutes, a solution of 83(mg) phenylboronic acid in ethanol (0.1ml) and a 2M aqueous solution of sodium carbonate (0.9ml) were added to the reaction mixture, and the mixture was refluxed. After 1 hour, the reaction mixture was cooled, ethyl acetate was added, and the mixture was filtered through celite. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The filtrate was concentrated, and the residue was subjected to flash silica gel column chromatography (40 ml of silica gel) and eluted with hexane-ethyl acetate ═ 3-1 to give crude crystals. This was washed with hexane to give the objective product (76mg) as colorless crystals.¹H-NMR(CDCl₃): 4.72(2H, s), 7.32-7.61(8H, m). mp 69-70 deg.C preparation example 11-32-chloro-1-methanesulfonyloxymethyl-4-phenylbenzene

The desired product (422mg) was obtained as a colorless oil by the same method as in preparation example 14-1 described below from 2-chloro-4-phenylbenzylalcohol (305 mg).¹H-NMR(CDCl₃): 3.05(3H, s), 5.39(2H, s), 7.34-7.60(7H, m), 7.66(1H, br). preparation 11-43- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile and 1- (2-chloro-4-phenylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

From 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (200mg), according to the same manner as in preparation example 14-2 described below, there were obtained pale yellow crystalline 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (163mg) and pale yellow amorphous 1- (2-chloro-4-phenylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (113 mg).

3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

¹H-NMR(CDCl₃)：2.62(3H，s)，5.64(2H，s)，6.74(1H，d，J＝8Hz)，7.31-7.56(6H，m)，7.62-7.70(2H，m)，8.10(1H，br d，J＝8Hz).MASS(ESI)：m/z 359(M+1)，mp 202-205℃

1- (2-chloro-4-phenylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

¹H-NMR(CDCl₃): 2.70(3H, br s), 5.52(2H, s), 6.60(1H, d, J ═ 8Hz), 7.31-7.60(8H, m), 7.70(1H, br d, J ═ 1Hz), mas (esi): m/z 359(M +1) preparation 11-53- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same method as in preparation example 10-2, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (159mg), the desired product (168mg) was obtained as colorless crystals.¹H-NMR(DMSO-d₆): 2.55(3H, s), 5.65(2H, s), 6.60(1H, d, J ═ 8Hz), 7.33-7.55(3H, m), 7.65(2H, br d, J ═ 8Hz), 7.85(1H, d, J ═ 1Hz), 8.00(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz). mass (esi): m/z 376(M-1) mp 238-

According to the same manner as in preparation example 14-2 below, from 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (200mg), pale brown crystalline 3- (1-bromonaphthalen-2-yl) methyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (139mg) and pale brown amorphous 1- (1-bromonaphthalen-2-yl) methyl-2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (96mg) were obtained.

3- (1-bromonaphthalen-2-yl) methyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

¹H-NMR(CDCl₃)：2.58(3H，s)，5.85(2H，s)，6.70(1H，d，J＝8Hz)，7.58(1H，br t，J＝8Hz)，7.62-7.71(3H，m)，7.81(1H，br d，J＝8Hz)，8.10(1H，d，J＝8Hz)，8.39(1H，br d，J＝8Hz).MASS(ESI)：m/z 377(M+1)mp 215-218℃

1- (1-bromonaphthalen-2-yl) methyl-2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

¹H-NMR(CDCl₃): 2.70(3H, s), 5.69(2H, s), 6.56(1H, d, J ═ 8Hz), 7.49-7.74(5H, m), 7.82(1H, d, J ═ 8Hz), 8.37(1H, d, J ═ 8Hz), mas (esi): m/z 377(M +1) preparation 12-23- (1-bromonaphthalen-2-yl) methyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 10-2, from 3- (1-bromonaphthalen-2-yl) methyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (138mg), the desired product (235mg) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆): 2.40(3H, s), 5.80(2H, s), 6.51(1H, d, J ═ 8Hz), 7.61(1H, br t, J ═ 8Hz), 7.75(1H, br t, J ═ 8Hz), 7.84(1H, d, J ═ 8Hz), 8.30(1H, d, J ═ 8Hz), mas (esi): m/z 394(M-1) mp > 250 deg.C preparation 13-12-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile and 2-methyl-1- (4-phenylbenzyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

According to the same manner as in preparation example 14-2 below, from 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (200mg), pale brown crystalline 2-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (140mg) and pale yellow amorphous 2-methyl-1- (4-phenylbenzyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (113mg) were obtained.

2-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

¹H-NMR(CDCl₃)：2.65(3H，s)，5.52(2H，s)，7.22-7.59(9H，m)，7.65(1H，d，J＝8Hz)，8.05(1H，d，J＝8Hz).MASS(ESI)：m/z 325(M+1)mp 225-226℃

2-methyl-1- (4-phenylbenzyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

¹H-NMR(CDCl₃): 2.72(3H, br s), 5.41(2H, s), 7.10(2H, d, J ═ 8Hz), 7.32-7.68(9H, m) mass (esi): m/z 325(M +1) preparation 13-22-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

The same procedures used in preparation example 14-2 were repeated except for using 2-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (135mg) to give the desired product (133mg) as colorless crystals.¹H-NMR(DMSO-d₆): 2.58(3H, s), 5.61(2H, s), 7.30(2H, d, J ═ 8Hz), 7.35(1H, d, J ═ 8Hz), 7.40-7.49(2H, m), 7.59-7.68(4H, m), 8.00(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), masss (esi): m/z 342(M-1) mp > 250 deg.C preparation of 14-14-bromo-2-chloro-1-methanesulfonyloxymethyl-benzene

Methanesulfonyl chloride (1.4ml) was added dropwise to a solution of 4-bromo-2-chlorobenzyl alcohol (3.56g) and anhydrous triethylamine (3ml) in anhydrous dichloromethane (36ml) under a nitrogen flow in an ice-water bath. After stirring for 1 hour, the reaction mixture was washed with water, a saturated aqueous sodium bicarbonate solution and a saturated brine, and then dried over anhydrous magnesium sulfate. The filtrate was concentrated to give the desired product (4.77g) as a pale brown solid.¹H-NMR(CDCl₃): 3.03(3H, s), 5.29(2H, s), 7.37(1H, d, J ═ 8Hz), 7.47(1H, dd, J ═ 8,1Hz), 7.60(1H, d, J ═ 1Hz), masss (esi): m/z 298(M-1) preparation 14-23- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile and 1- (4-bromo-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

Sodium hydride (70% in petroleum, 55mg) was added to a suspension of 2-methylimidazo [ 4, 5-b ] pyridine-5-carbonitrile (200mg) in N, N-dimethylformamide (2ml) in an ice-water bath, and the mixture was stirred for 30 minutes. To the reaction mixture was added 4-bromo-2-chlorobenzomethyl methanesulfonate (450mg), and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into water, and the product was extracted 3 times with ethyl acetate. The organic layer was collected, washed with water and saturated brine in this order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, 2 isomers, i.e., 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (Rf 0.4, 233mg) and 1- (4-bromo-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (Rf 0.1, 163mg), were isolated as white or pale yellow powders by silica gel column chromatography (dichloromethane/ethyl acetate: 5/1).

3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile:

¹H-NMR(CDCl₃)：2.58(3H，s)，5.52(2H，s)，6.55(1H，d，J＝8Hz)，7.27(1H，dd，J＝8 and 2Hz)，7.61(1H，d，J＝2Hz)，7.64(1H，d，J＝8Hz)，8.06(1H，d，J＝8Hz)Mass(ESI)：m/e 359，361(M-H)^-

1- (4-bromo-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile:

¹H-NMR(CDCl₃)：2.67(3H，s)，5.39(2H，s)，6.39(1H，d，J＝8Hz)，7.31(1H，dd，J＝8 and 2Hz)，7.53(2H，s)，7.65(1H，d，J＝2Hz)Mass(ESI)：m/e 359，361(M-H)^-preparation example 14-33- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

6N hydrochloric acid (2.5ml) was added to 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (226mg), and the mixture was refluxed for 1.5 hours. The reaction mixture was cooled with ice, adjusted to pH5 with a 1N aqueous solution of sodium hydroxide, and filtered to obtain a precipitate. This was dried under reduced pressure to give the desired product (226mg) as a white powder.¹H-NMR(DMSO-d₆)：2.51(3H，s)，5.58(2H，s)，6.52(1H，d，J＝8Hz)，7.43(1H，dd，J＝8 and 2Hz)，7.85(1H，d，J＝2Hz)，8.00(1H，d，J＝8Hz)，8.12(1H，d，J＝8Hz)Mass(ESI)：m/e 378，380(M-H)^-Preparation example 15-15-bromo-3- (2-bromo)-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine and 5-bromo-1- (2-bromo-4-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine

According to the same manner as in preparation example 14-2, from 5-bromo-2-methyl-1H-imidazo [ 4, 5-b ] pyridine (2.12g), 5-bromo-3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (2.30g) and 5-bromo-1- (2-bromo-4-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine (1.32g) were obtained as white powders.

5-bromo-3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine:

¹H-NMR(CDCl₃)：2.51(3H，s)，5.49(2H，s)，6.48(1H，d，J＝8Hz)，7.16(1H，dd，J＝8 and 2Hz)，7.43(1H，d，J＝8Hz)，7.65(1H，d，J＝2Hz)，7.89(1H，d，J＝8Hz)Mass(ESI)：m/e 414，416，418(1∶2∶1，M+H)⁺

5-bromo-1- (2-bromo-4-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine:

¹H-NMR(CDCl₃)：2.62(3H，s)，5.34(2H，s)，6.37(1H，d，J＝8Hz)，7.19(1H，dd，J＝8 and 2Hz)，7.29(2H，s)，7.68(1H，d，J＝2Hz)Mass(ESI)：m/e 414，416，418(1∶2∶1，M+H)⁺preparation example 15-23- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile

The desired product (268mg) was obtained as a pale yellow powder from 5-bromo-3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (2.07g) in the same manner as in preparation example 8-4.¹H-NMR(CDCl₃)：2.59(3H，s)，5.04(2H，s)，6.51(1H，d，J＝8Hz)，7.17(1H，dd，J＝8 and 2Hz)，7.66(1H，d，J＝8Hz)，7.68(1H，d，J＝2Hz)，8.10(1H，d，J＝8Hz)Mass(ESI)：m/e 361，363(M+H)⁺Preparation examples 15 to 3

3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

The same procedures used in preparation example 14-3 were repeated except for using 3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carbonitrile (253mg) to give the desired product (214mg) as a pale yellow powder.¹H-NMR(DMSO-d₆)：2.54(3H，s)，5.56(2H，s)，6.55(1H，d，J＝8Hz)，7.34(1H，dd，J＝8 and 2Hz)，7.90(1H，d，J＝2Hz)，8.04(1H，d，J＝8Hz)，8.18(1H，d，J＝8Hz)Mass(ESI)：m/e 378，380(M-H)^-Preparation example 16-12-Methylindolizine-6-carboxylic acid methyl ester

Methyl 6-methyl-3-pyridinecarboxylate (9.83g) and bromoacetone (11.8g) were mixed in acetone (98ml), and the mixture was refluxed for 20 hours. The solvent was distilled off under reduced pressure, and the residue was dissolved in methanol (98 ml). Sodium bicarbonate (16.4g) was added and heated under reflux for 24 hours. The reaction mixture was concentrated under reduced pressure, and the precipitate was filtered off with water. Recrystallization from hexane-ethyl acetate afforded the title product (5.94g) as a light yellow solid.¹H-NMR(CDCl₃)：2.31(3H，s)，3.89(3H，s)，6.29(1H，s)，7.06-7.29(3H，m)，8.63(1H，s)Mass(ESI)：m/e 190(M+H)⁺Preparation example 16-23- (2, 4-Dichlorobenzoyl) -2-methylindolizine-6-carboxylic acid methyl ester

4-Dichlorobenzoyl chloride (2.93g) was added to a suspension of anhydrous aluminum chloride (3.18g) in dichloromethane (19ml) under ice-water bath conditions, and stirred for 10 minutes. To the solution was added methyl 2-methylindolizine-6-carboxylate (1.89g), and the mixture was stirred at room temperature for 4 hours. The reaction solution was slowly poured into ice water, and the product was extracted with ethyl acetate. The organic layer was washed successively with water, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 5/1) to give the desired product (2.39g) as a pale yellow solid.¹H-NMR(CDCl₃)：1.85(3H，s)，3.95(3H，s)，6.39(1H，s)，7.25(1H，s)，7.29(1H，d，J＝8Hz)，7.37(1H，d，J＝8Hz)，7.41-7.52(2H，m)，7.76(1H，d，J＝8Hz)Mass(ESI)：m/e 362(M-H)^-Preparation example16-33- (2, 4-Dichlorophenylmethyl) -2-methylindolizine-6-carboxylic acid methyl ester

To a solution of methyl 3- (2, 4-dichlorobenzoyl) -2-methylindolizine-6-carboxylate (2.34g) in tetrahydrofuran (47ml) was added dropwise borane-dimethylsulfide complex (10.0M, 6.5ml) under ice-water bath conditions, and the mixture was stirred at room temperature for 4 hours. 1N hydrochloric acid (6.5ml) was carefully added dropwise to the reaction solution under ice-water bath conditions, and stirred at room temperature for 30 minutes. The reaction solution was neutralized with a saturated aqueous sodium bicarbonate solution, and the product was extracted with ethyl acetate 3 times. The organic layer was collected, washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 5/1) to give the desired product (490.4mg) as a pale yellow solid. ¹H-NMR(CDCl₃)：2.27(3H，s)，3.83(3H，s)，4.28(2H，s)，6.42(1H，d，J＝8Hz)，7.01(1H，dd，J＝8 and 2Hz)，7.13(1H，d，J＝8Hz)，7.24(1H，s)，7.30(1H，d，J＝8Hz)，7.44(1H，d，J＝2Hz)，8.29(1H，s)Mass(ESI)：m/e 348(M+H)⁺Preparation example 16-43- (2, 4-Dichlorophenylmethyl) -2-methylindolizine-6-carboxylic acid

The desired product (487mg) was obtained as a yellow powder from methyl 3- (2, 4-dichlorobenzyl) -2-methyl-indolizine-6-carboxylate (460mg) according to the same method as in production examples 4 to 7.¹H-NMR(DMSO-d₆): 2.24(3H, s), 4.38(2H, s), 6.46(1H, s), 6.58(1H, d, J. 8Hz), 7.03(1H, d, J. 8Hz), 7.27(1H, dd, J. 8 and 3Hz), 7.40(1H, d, J. 8Hz), 7.67(1H, d, J. 3Hz), 8.33(1H, s) preparation 17-13- (2, 4-dichlorobenzyl) -2-ethyl-7-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid ethyl ester

The desired product (210mg) was obtained from ethyl 2-ethyl-7-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (300mg) according to the same method as in preparation example 14-2.¹H-NMR(CDCl₃)：1.36(3H，t，J＝7Hz)，1.42(3H，t，J＝7Hz)，2.73(3H，s)，2.79(2H，q，J＝7Hz)，4.45(2H，q，J＝7Hz)，5.61(2H，s)，6.55(1H，d，J＝8Hz)，7.07(1H，dd，J＝8,1Hz)，7.45(1H，d，J＝1Hz)，7.95(1H，s).Mass(ESI): m/e 394(M +1) mp: 143 ℃ C. preparation example 17-23- (2, 4-Dichlorobenzyl) -2-ethyl-7-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

The desired product (181mg) was obtained from ethyl 3- (2, 4-dichlorobenzyl) -2-ethyl-7-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate according to the same method as in preparation 4-7.¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 7Hz), 2.76(3H, s), 2.87(2H, q, J ═ 7Hz), 5.53(2H, s), 6.49(1H, d, J ═ 8Hz), 7.11(1H, br d, J ═ 8Hz), 7.49(1H, br s), 8.05(1H, s). mass (esi): m/e 362(M-1) mp: 214 ℃ preparation example 18-12-Ethyl-7-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine 5-carboxylic acid ethyl ester

The desired product (294mg) was obtained from ethyl 2-ethyl-7-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (292mg) according to the same method as in preparation example 14-2.¹H-NMR(CDCl₃): 1.36(3H, t, J ═ 7Hz), 1.45(3H, t, J ═ 7Hz), 2.73(3H, s), 2.78(2H, q, J ═ 7Hz), 4.48(2H, q, J ═ 7Hz), 5.61(2H, s), 7.19-7.29(2H, m), 7.30-7.45(3H, m), 7.49-7.57(4H, m), 7.95(1H, s). masks (esi): m/e 400(M +1) mp: preparation of 18-22-ethyl-7-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid at 153 ℃ and 154 ℃

The desired product (249mg) was obtained from ethyl 2-ethyl-7-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (287mg) according to the same manner as in preparation examples 4 to 7.¹H-NMR(DMSO-d₆): 1.28(3H, t, J ═ 7Hz), 2.63(3H, s), 2.90(2H, q, J ═ 7Hz), 5.61(2H, s), 7.24(2H, d, J ═ 8Hz), 7.30-7.48(3H, m), 7.59-7.68(4H, m), 7.78(1H, s) mass (esi): m/e 370(M-1) mp 171-174 ℃ preparation of methyl 19-13- (4-bromo-2-chlorobenzoyl) -2-methylbenzo [ b ] thiophene-5-carboxylate

The desired product (297mg) was obtained as pale green crystals from methyl 2-methylbenzo [ b ] thiophene-5-carboxylate (191mg) according to the same method as in preparation example 1-1. ¹H-NMR(CDCl₃)：2.43(3H，s)，3.92(3H，s), 7.38(1H, d, J ═ 8Hz), 7.56(1H, d, J ═ 8Hz), 7.65(1H, s), 7.80(1H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz), 8.49(1H, s) preparation 19-23- (4-bromo-2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same manner as in preparation example 1-2, methyl 3- (4-bromo-2-chlorobenzoyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (280mg) was used to obtain the desired product (271mg) as white crystals.¹H-NMR(CDCl₃): 2.47(3H, s), 3.90(3H, s), 4.20(2H, s), 6.55(1H, d, J ═ 8Hz), 7.14(1H, dd, J ═ 2,8Hz), 7.58(1H, d, J ═ 3Hz), 7.83(1H, d, J ═ 8Hz), 7.93(1H, d, J ═ 8Hz), 8.13(1H, s) preparative example 19-33- (4-bromo-2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4-bromo-2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (255mg) was used to obtain the desired product (237mg) as white crystals.¹H-NMR(DMSO-d₆): preparation of 20-13- (2, 4-dichloro-5-fluorobenzoyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester (1H, d, J ═ 8Hz), 7.39(1H, dd, J ═ 2,8Hz), 7.77(1H, s), 7.82(1H, d, J ═ 8Hz), 8.01(1H, s), 8.03(1H, d, J ═ 8Hz), 2.52(3H, s), 4.22(2H, s), 6.72(1H, d, J ═ 8Hz)

The desired product (341mg) was obtained as pale green crystals from methyl 2-methylbenzo [ b ] thiophene-5-carboxylate (200mg) according to the same method as in preparation example 16-2.¹H-NMR(CDCl₃): 2.47(3H, s), 3.92(3H, s), 7.32(1H, d, J ═ 8Hz), 7.56(1H, d, J ═ 4Hz), 7.82(1H, d, J ═ 8Hz), 8.03(1H, d, J ═ 8Hz), 8.51(1H, s) preparation 20-23- (2, 4-dichloro-5-fluorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same manner as in preparation example 1-2, methyl 3- (2, 4-dichloro-5-fluorobenzoyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (318mg) was used to obtain the desired product (307mg) as white crystals.¹H-NMR(CDCl₃)：2.48(3H，s)，3.91(3H，s)，4.19(2H，s)，6.43(1H，d，J＝8Hz)，7.50(1H，dd，J＝2,7Hz)，7.84(1H，d, J ═ 8Hz), 7.96(1H, dd, J ═ 2, 8Hz), 8.10(1H, s) preparation of 20-33- (2, 4-dichloro-5-fluorobenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- (2, 4-dichloro-5-fluorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (290mg) was used to give the desired product (241mg) as white crystals.¹H-NMR(DMSO-d₆): 2.52(3H, s), 4.27(2H, s), 6.78(1H, d, J. RTM.9 Hz), 7.84(1H, d, J. RTM.8 Hz), 7.89(1H, d, J. RTM.7 Hz), 8.03(1H, d, J. RTM.7 Hz), 8.04(1H, s) preparation 21-13- ((3-chlorobenzo [ b ] thiophen-2-yl) carbonyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same manner as in preparation example 16-2, from methyl 2-methylbenzo [ b ] thiophene-5-carboxylate (200mg), the objective product (389mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): preparation of 2.56(3H, s), 3.87(3H, s), 7.48-7.63(2H, m), 7.82-8.05(4H, m), 8.37(1H, s) methyl 21-23- ((3-chlorobenzo [ b ] thiophen-2-yl) hydroxymethyl) -2-methylbenzo [ b ] thiophene-5-carboxylate

According to the same manner as in the following preparation example 35-5, methyl 3- ((3-chlorobenzo [ b ] thiophen-2-yl) carbonyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (380mg) was used to obtain the objective product (297mg) as white crystals.¹H-NMR(CDCl₃): 2.70(3H, s), 3.91(3H, s), 6.72(1H, s), 7.32-7.43(2H, m), 7.72-7.77(3H, m), 7.90(1H, d, J ═ 8Hz), 8.84(1H, s) preparation 21-33- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same manner as in preparation example 35-6 described below, methyl 3- ((3-chlorobenzo [ b ] thiophen-2-yl) hydroxymethyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (280mg) was used to obtain the objective product (266mg) as white crystals.¹H-NMR(CDCl₃): 2.61(3H, s), 3.92(3H, s), 2.47(2H, s), 7.30(1H, d, J ═ 8Hz), 7.41(1H, t, J ═ 8Hz), 7.60(1H, d, J ═ 7Hz), 7.78-7.82(2H, m), 7.94(1H, dd, J ═ 2, 8Hz), 8.41(1H, s) preparation 21-43- ((3-chlorobenzo [ b ] thiophene-2- Yl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (250mg) was used to obtain the desired product (243mg) as white crystals.¹H-NMR(DMSO-d₆): example 22-13- (1-bromonaphthalen-2-yl) carbonyl-2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester preparation 4.57(2H, s), 7.39(1H, t, J ═ 8Hz), 7.49(1H, t, J ═ 8Hz), 7.76(1H, d, J ═ 7Hz), 7.84(1H, d, J ═ 7Hz), 7.87(1H, d, J ═ 7Hz), 8.02(1H, d, J ═ 8Hz), 8.30(1H, s)

According to the same manner as in preparation example 16-2, methyl 2-methylbenzo [ b ] thiophene-5-carboxylate (200mg) was used to obtain the desired product (358mg) as pale green crystals.¹H-NMR(CDCl₃): 2.30(3H, s), 3.83(3H, s), 7, 48(1H, d, J ═ 8Hz), 7.62-7.72(2H.m), 7.80(1H, d, J ═ 8Hz), 7.90-8.03(3H, m), 8.38(1H, d, J ═ 8Hz), 8.73(1H, s) preparation 22-23- (1-bromonaphthalen-2-yl) methyl-2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same method as in preparation example 1-2, methyl 3- (1-bromonaphthoyl-2-yl) -2-methylbenzo [ b ] thiophene-5-carboxylate (342mg) was used to obtain the objective product (331mg) as white crystals. ¹H-NMR(CDCl₃): 2.49(3H, s), 3.85(3H, s), 4.52(2H, s), 6.84(1H, d, J ═ 8Hz), 7.48(1H, t, J ═ 8Hz), 7.55 to 7.63(2H, m), 7.74(1H, d, J ═ 8Hz), 7.83(1H, d, J ═ 8Hz), 7.93(1H, d, J ═ 8Hz), 8.23(1H, s), 8.39(1H, d, J ═ 8Hz), preparation 22-33- (1-bromonaphthalen-2-yl) methyl-2-methylbenzo [ b ] thiophene-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- (1-bromonaphthalen-2-yl) methyl-2-methylbenzo [ b ] thiophene-5-carboxylate (315mg) was used to give the desired product (284mg) as white crystals.¹H-NMR(DMSO-d₆)：2.57(3H，s)，4.53(2H，s)，6.94(1H，d，J＝8Hz)，7.57(1H，t，J＝7Hz)，7.70(1H，t，J＝7Hz)，7.78(1H，d，J＝8Hz)，7.83(1H，d，J＝8Hz)，7.90(1H，d，J＝8Hz)，Preparation of 23-14, 5-dibromo-2-methyl-1- (2- (trimethylsilyl) ethoxymethyl) imidazole (8.03 (1H, d, J ═ 8Hz), 8.08(1H, s), 8.30(1H, d, J ═ 8Hz)

4, 5-dibromo-2-methylimidazole (4.91g) was dissolved in N, N-dimethylformamide (50ml), and 60% sodium hydride (901mg) was slowly added under ice-water bath conditions. After stirring at room temperature for 1 hour, 2- (trimethylsilyl) ethoxychloromethane (3.75g) was slowly added dropwise under ice-water bath conditions, and stirred at room temperature overnight. After the solvent was distilled off under reduced pressure, ethyl acetate was added to the residue, which was washed with a saturated aqueous sodium bicarbonate solution and then with brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 3/1) to give the desired product (7.6g) as a colorless oil. ¹H-NMR(CDCl₃): 0.00(9H, s), 0.92(2H, t, J ═ 8Hz), 2.47(3H, s), 3.55(2H, t, J ═ 8Hz), 5.24(2H, s) preparation 23-24-bromo-2-methyl-1- (2- (trimethylsilyl) ethoxymethyl) imidazole-5-carbaldehyde

4, 5-dibromo-2-methyl-1- (2- (trimethylsilyl) ethoxymethyl) imidazole (29.2g) was dissolved in tetrahydrofuran (250ml), and a 1.63N N-butyllithium/hexane solution (58.1ml) was added dropwise thereto at-55 ℃ to-60 ℃ over 20 minutes. After stirring at-60 ℃ for 30 minutes, N-dimethylformamide (58g) was slowly added dropwise at-55 ℃ to-60 ℃ and stirred at room temperature for 1 hour. Saturated brine was added, extraction was performed with ethyl acetate, and then the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 3/1) to give the desired product (18.5g) as a pale yellow oil.¹H-NMR(CDCl₃): preparation of example 23-32-methyl-1- (2- (trimethylsilyl) ethoxymethyl) -1H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid ethyl ester 0.00(9H, s), 0.91(2H, t, J ═ 8Hz), 2.52(3H, s), 3.58(2H, t, J ═ 8Hz), 5.70(2H, s), 9.71(1H, s)

2.68M sodium ethoxide was dissolved in ethanol (50ml), and an ethanol solution (25ml) of ethyl thioglycolate was added. To which 4-bromo-2-methyl-1- (2- (trimethyl) is added Phenylsilyl) ethoxymethyl) imidazole-5-carbaldehyde (3.16g) in ethanol (150ml) was stirred at 80 ℃ for 2 hours. The solvent was distilled off under reduced pressure, water was added, and extraction was performed 2 times with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 9/1). Hexane was added to the purified product, and the crystals were filtered to give a pale brown crystalline desired product (765mg)¹H-NMR(CDCl₃): 0.00(9H, s), 0.94(2H, t, 8Hz), 1.43(3H, t, 8Hz), 2.15(3H, s), 3.56(2H, t, 8Hz), 4.40(2H, q, 8Hz), 5.42(2H, s), 7.64(1H, s) preparation 23-42-methylthiothieno [ 2, 3-d ] imidazole-5-carboxylic acid ethyl ester

Ethyl 2-methyl-1- (2- (trimethylsilyl) ethoxymethyl) -1H-thieno [ 2, 3-d ] imidazole-5-carboxylate (745mg) was dissolved in ethanol (10ml), and 6N hydrochloric acid (10ml) was added to the solution, followed by refluxing under heating for 1 hour. Under the condition of ice-water bath, saturated sodium bicarbonate aqueous solution is added to make the mixture reach alkalescence, and ethyl acetate is used for extraction. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, followed by washing with brine, followed by drying over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain the objective product (370mg) as white crystals. ¹H-NMR(CDCl₃): 1.39(3H, t, 7Hz), 2.56(3H, s), 4.36(2H, q, 7Hz), 7.62(1H, s) preparation 23-51- (2, 4-dichlorobenzyl) -2-methyl-1H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid ethyl ester and 3- (2, 4-dichlorobenzyl) -2-methyl-3H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid ethyl ester

According to the same manner as in preparation example 14-2, from ethyl 2-methylthiophene [ 2, 3-d ] imidazole-5-carboxylate (350mg), ethyl 1- (2, 4-dichlorobenzyl) -2-methyl-1H-thieno [ 2, 3-d ] imidazole-5-carboxylate (340mg) and ethyl 3- (2, 4-dichlorobenzyl) -2-methyl-3H-thieno [ 2, 3-d ] imidazole-5-carboxylate (168mg) were obtained as white crystals. NOE was used to determine the respective structures.

1- (2, 4-Dichlorophenylmethyl) -2-methyl-1H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid ethyl ester

¹H-NMR(CDCl₃)：1.36(3H，t，7Hz)，2.54(3H，s)，4.32(2H，q，8Hz)，5.29(2H，s)，6.62(1H，d，8Hz)，7.17(1H，dd，2.8Hz)，7.38(1H，s)，7.47(1H，d，2Hz)

3- (2, 4-Dichlorophenylmethyl) -2-methyl-3H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid ethyl ester

¹H-NMR(CDCl₃): 1.36(3H, t, 8Hz), 2.60(3H, s), 4.32(2H, q, 8Hz), 5.23(2H, s), 6.97(1H, d, 8Hz), 7.29(1H, dd, 2, 8Hz), 7.47(1H, d, 2Hz), 7.80(1H, d, 2Hz) preparation 23-61- (2, 4-dichlorobenzyl) -2-methyl-1H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid

The desired product (151mg) was obtained as white crystals from ethyl 1- (2, 4-dichlorobenzyl) -2-methyl-1H-thieno [ 2, 3-d ] -5-carboxylate (170mg) according to the same method as in preparation examples 4 to 7.¹H-NMR(DMSO-d₆): preparation of 23-73- (2, 4-dichlorobenzyl) -2-methyl-3H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid from 2.48(3H, s), 5.48(2H, s), 6.97(1H, d, 8Hz), 7.44(1H, dd, 2, 8Hz), 7.50(1H, s), 7.73(1H, d, 2Hz)

The desired product (112mg) was obtained as white crystals from ethyl 3- (2, 4-dichlorobenzyl) -2-methyl-3H-thieno [ 2, 3-d ] -5-carboxylate (130mg) according to the same method as in preparation examples 4 to 7.¹H-NMR(DMSO-d₆): 2.57(3H, s), 5.40(2H, s), 7.50(1H, d, 8Hz), 7.56(1H, dd, 2, 8Hz), 7.65(1H, s), 7.77(1H, d, 2Hz) preparation of ethyl 24-16-amino-5-nitronicotinate

According to the same manner as in preparation example 4-5, from 6-amino-5-nitronicotinic acid (18.2g), the objective product (9.2g) was obtained as yellow crystals.¹H-NMR(CDCl₃): 1.41(3H, t, J ═ 7Hz), 4.40(2H, q, J ═ 7Hz), 8.95(1H, d, J ═ 2Hz), 9.01(1H, s) mass (esi): m/z 210(M-1) preparation 24-25, 6-bisAmino nicotinic acid ethyl ester

Reduced iron (496mg) was added to a suspension of ethyl 6-amino-5-nitro-5-nicotinate (500mg), ammonium chloride (50mg) in water (0.5ml), and ethanol (4.5ml) at 50 ℃ and then heated under reflux. After 3 hours, 200mg of reduced iron was added thereto, and the mixture was refluxed for 3 hours. After the reaction solution was cooled, the reaction solution was filtered through celite, and washed with chloroform. The filtrate was washed with water, and the organic layer was dried over anhydrous magnesium sulfate and filtered. After concentration, the residue was crystallized from isopropyl ether to give the desired product as reddish brown crystals (307 mg). ¹H-NMR(CDCl₃): 1.38(3H, t, J ═ 7Hz), 3.30(2H, br), 4.32(2H, q, J ═ 7Hz), 4.70(2H, br), 7.49(1H, d, J ═ 1Hz), 8.37(1H, d, J ═ 1Hz). mas (esi): m/z 182(M +1) preparation of 24-36-amino-5- (1-aza-2- (2, 4-dichlorophenyl) vinyl) nicotinic acid ethyl ester

A mixture of ethyl 5, 6-diaminonicotinate (3.17g), benzaldehyde (4g) and molecular sieves 4. ANG. (15g) in tetrahydrofuran (60ml) was heated under reflux for 2 days. The reaction mixture was filtered, and the residue was concentrated and crystallized from ethyl acetate to obtain the desired product (2.89g) as yellow crystals.¹H-NMR(CDCl₃): 1.38(3H, t, J ═ 7Hz), 3.30(2H, br), 4.32(2H, q, J ═ 7Hz), 4.70(2H, br), 7.49(1H, d, J ═ 1Hz), 8.37(1H, d, J ═ 1Hz). mas (esi): m/z 182(M +1) preparation of ethyl 24-46-amino-5- (2, 4-dichlorobenzylamino) nicotinate

To a suspension of ethyl 6-amino-5- (1-aza-2- (2, 4-dichlorophenyl) vinyl) nicotinate (2.88g) in ethanol (30ml) was added sodium borohydride (644mg) at room temperature, followed by stirring. After 3 hours, water was added to the reaction mixture and CHCl was used₃And (4) extracting. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and filtered. After concentration, the residue was crystallized from ethyl acetate to obtain the desired product (1.68g) as yellow crystals. The mother liquor was concentrated and crystallized from isopropyl ether to give the desired product (594mg) as yellow crystals. ¹H-NMR(CDCl₃)：1.37(3H，t，J＝7Hz)，3.49(1H，br t，J＝6Hz)，4.32(2H，q，J＝7Hz)，4.40(2H，d，J＝6Hz)，4.69(2H，br s)，7.22(1H，d，J＝8Hz)，7.31(1H，d，J＝8Hz)，7.39(1H, br s), 7.45(1H, d, J ═ 1Hz), 8.35(1H, d, J ═ 1Hz), mas (esi): m/z 340(M +1) preparation 24-51- (2, 4-Dichlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-6-carboxylic acid ethyl ester

A suspension of ethyl 6-amino-5- (2, 4-dichlorobenzylamino) nicotinate (300mg) and acetic acid (132mg) in polyphosphoric acid (6g) was heated to 100 ℃. After 2 hours, the reaction was cooled and ice (5g) was added. Neutralized with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and filtered. After concentration, the residue was crystallized from isopropyl ether to give the desired product (288mg) as pale brown crystals.¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 7Hz), 2.64(3H, s), 4.41(2H, q, J ═ 7Hz), 5.41(2H, s), 6.39(1H, d, J ═ 8Hz), 7.11(1H, dd, J ═ 8,2Hz), 7.50(1H, s), 8.12(1H, br s), 9.20(1H, d, J ═ 2Hz). mas esi (esi): m/z 364(M +1) preparation 24-61- (2, 4-Dichlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-6-carboxylic acid

According to the same manner as in preparation example 4-7, from ethyl 1- (2, 4-dichlorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-6-carboxylate (337mg), the desired product (309mg) was obtained as pale brown crystals. ¹H-NMR(DMSO-d₆): 2.57(3H, s), 5.68(2H, s), 6.68(1H, d, J ═ 8Hz), 7.34(1H, dd, J ═ 8, 2Hz), 7.74(1H, d, J ═ 2Hz), 8.35(1H, d, J ═ 2Hz), 8.91(1H, s). mas (esi): m/z 334(M-1) preparation of 25-1 Ethyl-2-chloro-3-pyridylcarbamate

Ethyl chlorocarbonate (9ml) was added dropwise to a mixed solution of 3-amino-2-chloropyridine (10g) in a 1N aqueous solution of sodium hydroxide (156ml) and 1, 4-dioxane (100ml) under ice-cooling at 10 to 20 ℃. After 10 minutes, stir at room temperature. After 2 hours, ethyl chlorocarbonate (4ml) was added. After 4 hours, 5 hours and 6 hours, ethyl chlorocarbonate (4ml) and an aqueous sodium hydroxide solution (40ml) were added, respectively. After standing overnight, water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. Concentrating the filtrate, and subjecting to flash silica gel column chromatography (silica gel 4)00ml) was added to the residue, which was eluted with hexane-ethyl acetate 5-1 to give the desired product (14.8g) as a colorless solid.¹H-NMR(CDCl₃): 1.34(3H, t, J ═ 7Hz), 4.28(2H, q, J ═ 7Hz), 7.11(1H, br s), 7.25(1H, dd, J ═ 8, 5Hz), 8.08(1H, d, J ═ 5Hz), 8.50(1H, d, J ═ 8Hz), mass (esi): m/z 199(M-1) preparation 25-2 Ethyl-2- (1-propyn-1-yl) -3-pyridylcarbamate

Ethyl-2-chloro-3-pyridylcarbamate (13.5g), tributyl (1-propyn-1-yl) tin (22g), and tetrakis (triphenylphosphine) palladium (O) (1.56g) were added to a suspension of lithium chloride (7g) in 1, 4-dioxane (135ml), and the mixture was refluxed. After 1 hour and 30 minutes, the reaction mixture was cooled, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and a saturated brine, and dried over anhydrous magnesium sulfate. The filtrate was concentrated, and the residue was subjected to flash silica gel column chromatography (silica gel 400ml), which was eluted with hexane-ethyl acetate ═ 2-1 to give the objective product (10.9g) as a pale yellow solid.¹H-NMR(CDCl₃): 1.36(3H, t, J ═ 7Hz), 2.19(3H, s), 4.25(2H, q, J ═ 7Hz), 7.20(1H, dd.j ═ 8,5Hz), 7.33(1H, br s), 8.20(1H, d, J ═ 5Hz), 8.45(1H, br d, J ═ 8Hz), mas (esi): m/z 205(M +1) mp 90-91 deg.C preparation of 25-32-methylpyrrolo [ 3, 2-b ] pyridine

To an ethanol solution of ethyl-2- (1-propyn-1-yl) -3-pyridylcarbamate (10.9g) was added a 21% ethanol solution (50ml) of sodium ethoxide, and the mixture was refluxed. After 1 hour and 30 minutes, the reaction mixture was cooled, water was added thereto, and the mixture was extracted with dichloromethane 3 times. The organic layer was dried over anhydrous magnesium sulfate and filtered. After concentration, the residue was crystallized from ethyl acetate to give the desired product (6.5g) as pale brown crystals. ¹H-NMR(CDCl₃): 2.41(3H, s), 6.23(1H, s), 6.97(1H, dd, J ═ 8,5Hz), 7.60(1H, d, J ═ 8Hz), 8.19(1H, br d, J ═ 5Hz), masss (esi): m/z 133(M +1) mp 193-195 deg.C preparation example 25-43- (2, 4-dichlorobenzoyl) -2-methylpyrrolo [ 3, 2-b ] pyridine

According to the same method as in preparation example 16-2, from 2-methylpyrrolo [ 3, 2-b ] pyridine (500mg) was obtained a colorless solidThe desired product (1.23g) was in the form of a powder.¹H-NMR(DMSO-d₆): 2.75(3H, s), 7.07(1H, dd, J ═ 8,5Hz), 7.38(1H, d, J ═ 8Hz), 7.48(1H, d, J ═ 8Hz), 7.65(1H, s), 7.74(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 5Hz). mas (esi): m/z 303(M-1) preparation 25-53- ((2, 4-dichlorophenyl) hydroxymethyl) -2-methylpyrrolo [ 3, 2-b ] pyridine

The desired product (850mg) was obtained as a colorless solid from 3- (2, 4-dichlorobenzoyl) -2-methylpyrrolo [ 3, 2-b ] pyridine (1.11g) according to the same method as in preparation example 35-5 described below.¹H-NMR(DMSO-d₆): 2.28(3H, s), 5.69(1H, d, J ═ 5Hz), 6.30(1H, d, J ═ 5Hz), 6.98(1H, dd, J ═ 8,5Hz), 7.41 to 7.48(2H, m), 7.58(1H, d, J ═ 8Hz), 8.05(1H, d, J ═ 8Hz), 8.20(1H, d, J ═ 5Hz), mas esi (esi): m/z 307(M +1) mp 195-supple preparation 25-63- (2, 4-dichlorobenzyl) -2-methylpyrrolo [ 3, 2-b ] pyridine at 197 ℃

From 3- ((2, 4-dichlorophenyl) hydroxymethyl) -2-methylpyrrolido [ 3, 2-b ] pyridine (840mg), the objective product (580mg) was obtained as a colorless solid in the same manner as in preparation example 35-6 described below.¹H-NMR(DMSO-d₆): 2.39(3H, s), 4.18(2H, s), 6.98(1H, dd, J ═ 8, 5Hz), 7.21-7.33(2H, m), 7.62(1H, d, J ═ 2Hz), 8.06(1H, br d, J ═ 8Hz), 8.38(1H, d, J ═ 5Hz). mas (esi): m/z 291(M +1) mp 228-

The same procedure as in preparation 14-2 was repeated, except for using 3- (2, 4-dichlorobenzyl) -2-methylpyrrolido [ 3, 2-b ] pyridine (528mg) to give the desired product (405mg) as colorless crystals.¹H-NMR(CDCl₃): 1.50(3H, t, J ═ 7Hz), 2.58(3H, s), 4.21(2H, s), 4.52(2H, q, J ═ 7Hz), 6.96(1H, d, J ═ 8Hz), 7.02(1H, dd, J ═ 8, 1Hz), 7.19(1H, dd, J ═ 8, 5Hz), 7.39(1H, d, J ═ 1Hz), 8.32(1H, d, J ═ 8Hz), 8.49(1H, d, J ═ 5Hz), mas (esi): m/z 363(M +1) mp 92-93 deg.C preparation of 25-83- (2, 4-dichlorobenzyl) -2-methylpyrrolo [ 3, 2-b ] pyridine-1-carboxylic acidEthyl ester N-oxide

To a solution of ethyl 3- (2, 4-dichlorobenzyl) -2-methylpyrrolido [ 3, 2-b ] pyridine-1-carboxylate (400mg) in chloroform (6ml) was added m-chloroperbenzoic acid (462mg) at room temperature, and the mixture was stirred overnight. The reaction mixture was subjected to flash silica gel column chromatography (silica gel, 40ml), and the residue was eluted with ethyl acetate, then eluted with ethyl acetate-methanol (10-1) and then crystallized from ethyl ether to give the desired product (417mg) as colorless crystals. ¹H-NMR(CDCl₃): 1.50(3H, t, J ═ 7Hz), 2.51(3H, s), 4.53(2H, q, J ═ 7Hz), 4.61(2H, s), 6.96(1H, d, J ═ 8Hz), 7.01-7.11(2H, m), 7.39(1H, s), 8.00-8.09(2H, m) mass (esi): m/z 379(M +1) mp 126-

Trimethylsilyl cyanide (704mg) was added to a suspension of ethyl 3- (2, 4-dichlorobenzyl) -2-methylpyrrolido [ 3, 2-b ] pyridine-1-carboxylate N-oxide (414mg) in anhydrous triethylamine (4ml) under a nitrogen stream at room temperature, and the mixture was refluxed for 1 night. The reaction solution was cooled, and a saturated aqueous sodium bicarbonate solution was added. Extracted with ethyl acetate, washed with water and brine. Dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated, and the residue was subjected to flash silica gel column chromatography (80 ml of silica gel), eluted with hexane-ethyl acetate ═ 5-1 and crystallized from isopropyl ether to give the desired product (204mg) as colorless crystals.¹H-NMR(CDCl₃): 1.51(3H, t, J ═ 7Hz), 2.62(3H, s), 4.21(2H, s), 4.55(2H, q, J ═ 7Hz), 7.05-7.15(2H, m), 7.58(1H, d, J ═ 8Hz), 8.31(1H, d, J ═ 8Hz), mas (esi): m/z 388(M +1) mp 112-

A solution of ethyl 3- (2, 4-dichlorobenzyl) -5-cyano-2-methylpyrrolo [ 3, 2-b ] pyridine-1-carboxylate (180mg) in acetic acid (1ml) and concentrated hydrochloric acid (1ml) was refluxed with heating. After the reaction overnight, concentrated hydrochloric acid (1ml) was added and heated under reflux for 10 hours. The reaction solution was cooled, the pH was adjusted to 7 with 30% aqueous sodium hydroxide solution, stirred for 2 hours, filtered and crystals were collected,yellow crystalline desired product (135mg) was obtained.¹H-NMR(DMSO-d₆): 2.37(3H, s), 4.19(2H, s), 7.05(1H, d, J ═ 8Hz), 7.23(1H, dd, J ═ 8, 1Hz), 7.60(1H, d, J ═ 1Hz), 7.85(2H, s) mass (esi): m/z 333(M-1) mp 235-

According to the same manner as in preparation example 14-2, from 5-bromo-2-methyl-1H-imidazo [ 4, 5-b ] pyridine (305mg), 5-bromo-3- (4-chloro-2-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (200mg) as pale yellow crystals, 5-bromo-1- (4-chloro-2-methoxybenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine (138mg) as pale brown oil were obtained.

5-bromo-3- (4-chloro-2-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

¹H-NMR(CDCl₃)：2.69(3H，s)，3.86(3H，s)，5.41(2H，s)，6.85-6.95(3H，m)，7.45(1H，d，J＝8Hz)，7.92(1H，d，J＝8Hz).MASS(ESI)：m/z 368(M+1)mp 149-150℃

5-bromo-1- (4-chloro-2-methoxybenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine

¹H-NMR(CDCl₃): 2.67(3H, s), 3.81(3H, s), 5.25(2H, s), 6.68(1H, d, J ═ 8Hz), 6.84-6.91(2H, m), 7.26(1H, d, J ═ 8Hz), 7.38(1H, d, J ═ 8Hz) mas (esi): m/z 368(M +1) preparation 26-23- (4-chloro-2-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

To a solution of 5-bromo-3- (4-chloro-2-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (200mg) in anhydrous methanol (1.8ml) and anhydrous N, N-dimethylformamide (2ml) were added anhydrous triethylamine (129ml), palladium acetate (35mg), 1, 3-bis (diphenylbenzene) in an autoclavePhosphinyl) propane (72 mg). After 4 times of replacement with carbon monoxide, the mixture was stirred at 85 ℃ under 10 atmospheres. After 18 hours, the reaction solution was cooled, water was added thereto, and extraction was performed with ethyl acetate. The organic layer was washed with water 3 times, then with saturated brine, and then dried over anhydrous magnesium sulfate. Flash silica gel column chromatography (40 ml silica gel) was performed, and the product was eluted with dichloromethane-methanol (50-1) and then crystallized from ethanol to give the desired product as pale yellow crystals (148 mg).¹H-NMR(CDCl₃): 2.70(3H, s), 3.86(3H, s), 4.00(3H, s), 5.53(2H, s), 6.81-6.90(2H, m), 6.98(1H, br d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), 8.17(1H, d, J ═ 8Hz). mas (esi): m/z 346(M +1), mp 166-

According to the same manner as in preparation example 4-7, from methyl 3- (4-chloro-2-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (144mg), the desired product (105mg) was obtained as colorless crystals.¹H-NMR(DMSO-d₆): 2.52(3H, s), 3.90(3H, s), 5.44(2H, s), 6.62(1H, d, J ═ 8Hz), 6.89(1H, dd, J ═ 8, 1Hz), 7.15(1H, d, J ═ 1Hz), 7.98(1H, d, J ═ 8Hz), 8.09(1H, d, J ═ 8Hz), mas (esi): m/z 330(M-1) mp 243-

According to the same manner as in preparation example 14-2, from 5-bromo-2-methyl-1H-imidazo [ 4, 5-b ] pyridine (305mg), a mixture (399mg) of 5-bromo-3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine and 5-bromo-1- (4-chloro-2-methylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine was obtained as pale brown solids. The resulting mixture was used in the following reaction without separating the isomer. Preparation example 27-23- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (4-chloro-2-methylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 26-2, from a mixture (390mg) of 5-bromo-3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine and 5-bromo-1- (4-chloro-2-methylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine, colorless crystals of methyl 3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (148mg), brown powder of 1- (4-chloro-2-methylbenzyl) -2-methyl-1H-imidazo [ 4 ], 5-b ] pyridine-5-carboxylic acid methyl ester (87 mg).

3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)：2.41(3H，s)，2.56(3H，s)，4.00(3H，s)，5.53(2H，s)，6.44(1H，d，J＝8Hz)，7.03(1H，br d，J＝8Hz)，7.22(1H，br s)，8.12(1H，d，J＝8Hz)，8.19(1H，d，J＝8Hz).MASS(ESI)：m/z 330(M+1)，mp 175-176℃

1- (4-chloro-2-methylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃): 2.38(3H, s), 2.65(3H, s), 4.01(3H, s), 5.30(2H, s), 6.48(1H, d, J ═ 8Hz), 7.05(1H, br d, J ═ 8Hz), 7.26(1H, br s), 7.48(1H, d, J ═ 8Hz), 8.06(1H, d, J ═ 8Hz), mas (esi): m/z 330(M +1) preparation 27-33- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (163mg) was used to give the desired product (144mg) as colorless crystals. ¹H-NMR(DMSO-d₆)：2.52(3H，s)，2.45(3H，s)，2.49(3H，s)，5.51(2H，s)，6.31(1H，d，J＝8Hz)，7.10(1H，br d，J＝8Hz)，7.37(1H，br s)，8.00(1H，d，J＝8Hz)，8.11(1H，d，J＝8Hz).MASS(ESI)：m/z 314(M-1)mp 219-212℃Preparation 28-15-bromo-3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine and 5-bromo-1- (2-chloro-4-phenylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine

According to the same manner as in preparation example 14-2, from 5-bromo-2-methyl-1H-imidazo [ 4, 5-b ] pyridine (800mg), colorless crystals of 5-bromo-3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (883mg) and pale yellow crystals of 5-bromo-3- (2-chloro-4-phenylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine (681mg) were obtained.

5-bromo-3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

¹H-NMR(CDCl₃)：2.52(3H，s)，5.59(2H，s)，6.64(1H，br d，J＝8Hz)，7.30-7.47(5H，m)，7.49-7.54(2H，m)，7.66(1H，br s)，7.85(1H，d，J＝8Hz).MASS(ESI)：m/z 414(M+1)，mp 150-155℃

5-bromo-1- (2-chloro-4-phenylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine

¹H-NMR(CDCl₃): 2.67(3H, s), 5.44(2H, s), 6.57(1H, d, J ═ 8Hz), 7.24-7.55(8H, m), 7.69(1H, s) mass (esi): m/z 414(M +1), mp 181-

The desired product (504mg) was obtained as pale yellow crystals from 5-bromo-3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (822mg) according to the same method as in preparation example 26-2.¹H-NMR(CDCl₃): 2.60(3H, s), 4.00(3H, s), 5.73(2H, s), 6.71(1H, d, J ═ 8Hz), 7.30-7.54(6H, m), 7.67(1H, br), 8.10(1H, d, J ═ 8Hz), 8.18(1H, d, J ═ 8Hz). mas (esi): m/z 392(M +1) mp 200-

According to the same manner as in preparation example 4-7, from methyl 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (500mg), the desired product (403mg) was obtained as colorless crystals.¹H-NMR(DMSO-d₆): 2.55(3H, s), 5.65(2H, s), 6.60(1H, d, J ═ 8Hz), 7.33-7.55(3H, m), 7.65(2H, br d, J ═ 8Hz), 7.85(1H, d, J ═ 1Hz), 8.00(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz). mass (esi): m/z 376(M-1) mp 238-and 243 ℃ preparation of example 29-15-bromo-p-methoxybenzaldehyde

5-Bromosalicylaldehyde (25g, 124mmol) was dissolved in acetone (300ml), anhydrous potassium carbonate (17.2g, 124mmol) was added, and dimethyl sulfate (15.7g, 124mmol) was added dropwise over 45 minutes while heating and slightly refluxing. After the dropwise addition, the mixture was refluxed for 1 hour, cooled, and distilled under reduced pressure to remove acetone. Toluene and water were added to the residue, and the toluene layer was separated, and the aqueous layer was extracted with toluene. The organic layers were combined, washed with water, and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the desired product (27.3g, quantitative) as colorless crystals. Preparation example 29-2 (5-bromo-2-methoxyphenyl) acetone

A mixture of 5-bromop-methoxybenzaldehyde (19.4g, 90mmol), toluene (25ml), nitroethane (8.1g, 108mmol), butylamine (2.0g, 27mmol) was heated under vigorous reflux in a Dean-Stark distillation tube, while removing the water of reaction. In this process, n-butylamine (4.5ml) and nitroethane (4ml) were further added in portions and reacted for 6 hours. Then, the reaction solution was cooled, followed by addition of toluene and 3N hydrochloric acid for extraction, and the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give a brown oil containing 3- (2-nitropropene-1-yl) -4-methoxybromobenzene. This oil was dissolved in toluene (30ml), an aqueous solution (30ml) of iron (III) chloride 6 hydrate (1.0g) was added, then iron powder (15.1g, 270mmol) was added, and concentrated hydrochloric acid (37.5ml, 450mmol) was added dropwise thereto over 2 hours while heating to 75 ℃. After the completion of the dropwise addition, the mixture was further stirred at 75 ℃ for 1 hour. Cooling, filtering to remove insoluble substances, separating the filtrate, and adding toluene The aqueous layer was extracted. The organic layers were combined, washed with 3N hydrochloric acid and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: methane/ethyl acetate 4/1) to give the desired product (6.9g, 33%) as a colorless oil.¹H-NMR(CDCl₃δ ppm): 7.36(1H, dd, J ═ 2.4 and 8.7Hz), 7.24(1H, d, J ═ 2.4Hz), 6.75(1H, d, J ═ 9.0Hz), 3.78(3H, s), 3.63(2H, s), 2.15(3H, s), preparation 29-35-bromo-2-methylbenzo [ b ] furan

(5-bromo-2-methoxyphenyl) acetone (6.6g, 28.6mmol) was dissolved in dichloromethane (50ml), cooled to-70 ℃ and a 1M solution of boron tribromide in dichloromethane (28.6ml, 28.6mmol) was added dropwise thereto over 15 minutes. After the completion of the dropwise addition, the temperature was raised to room temperature, and the mixture was stirred for 1.5 hours. The reaction mixture was placed in an ice-water bath, water (50ml) was added thereto, insoluble matter was removed by filtration, and the filtrate was separated, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered to remove the drying agent, and concentrated under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (eluent: methane/ethyl acetate 30/1) to obtain the desired product (3.45g, 57%) as a colorless liquid. ¹H-NMR(CDCl₃δ ppm): 7.58(1H, d, J ═ 1.8Hz), 7.29(1H, dd, J ═ 1.8 and 8.6Hz), 7.26(1H, d, J ═ 8.3Hz), 6.31(1H, d, J ═ 0.7Hz), 2.45(3H, s), preparation 29-45-carboxy-2-methylbenzo [ b ] furan

Magnesium (2.34g, 97mmol) was suspended in diethyl ether and a mixture of 5-bromo-2-methylbenzo [ b ] furan (3.4g, 16.1mmol) and methyl iodide (6.86g, 48.3mmol) in diethyl ether (50ml) was added dropwise while continuing to slightly reflux. About 50 minutes was required for the dropwise addition. After the end of the dropwise addition, the mixture was refluxed for 30 minutes and then cooled in a dry ice-acetone bath. The pulverized dry ice was added to diethyl ether, and the reaction solution was slowly added thereto while stirring. 2N hydrochloric acid was added to the reaction solution, and after stirring, the organic layer obtained by separation was extracted with a 2N aqueous solution (100ml) of sodium hydroxide. The aqueous layer was made acidic with concentrated hydrochloric acid, and the precipitated crystals were dissolved in diethyl ether. Washing with saturated saline solutionThe organic layer was dried over anhydrous sodium sulfate. After removing the drying agent by filtration, the filtrate was concentrated under reduced pressure to give the objective product (1.9g, 67%) as colorless crystals.¹H-NMR(DMSO-d₆δ ppm: 8.28(1H, d, J ═ 1.5Hz), 8.01(1H, dd, J ═ 1.7 and8.5Hz), 7.45(1H, d, J ═ 8.6Hz), 6.46(1H, s), 2.48(3H, s), preparation 29-55- (methoxycarbonyl) -2-methylbenzo [ b ] furan

5-carboxy-2-methylbenzo [ b ] furan (1.9g, 10.7mmol) was dissolved in methanol (50ml), and concentrated sulfuric acid (0.1ml) was added thereto, followed by heating and refluxing for 14 hours. After cooling, a saturated aqueous sodium bicarbonate solution was added, methanol was removed by distillation under the reduced pressure, and the residue was extracted with methyl tert-butyl ether. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the drying agent, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: methane/ethyl acetate 9/1) to give the desired product (1.66g, 81%) as colorless crystals.¹H-NMR(CDCl₃δ ppm): 8.20(1H, d, J ═ 1.4Hz), 7.93(1H, dd, J ═ 1.5 and 8.5Hz), 7.42(1H, d, J ═ 8.5Hz), 6.43(1H, d, J < 1Hz), 3.93(3H, s), 2.47(SH, d, J ═ 0.6Hz), preparation 29-63- (2, 4-dichlorobenzyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan

Aluminum chloride (2.52g, 18.9mmol) was suspended in methylene chloride (25ml), and 2, 4-dichlorobenzoyl chloride (1.98g, 9.5mmol) and then 5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (1.5g, 7.9mmol) were added thereto, followed by stirring at room temperature for 1.5 hours. The reaction solution was poured into ice water, and ethyl acetate was added thereto for extraction. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate 2 times, then with saturated brine and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the desired product (2.9g, quantitative) as colorless crystals. ¹H-NMR(CDCl₃δ ppm): 8.28(1H, d, J ═ 1.4Hz), 8.04(1H, dd, J ═ 1.5 and 8.4Hz), 7.54(1H, d, J ═ 1.8Hz), 7.49(1H, dd, J ═ 0.6 and 8.3Hz), 7.43(1H, dd, J ═ 1.9 and 7.9Hz), 7.37(1H, d, J ═ 8.1Hz), 3.91(3H, s), 2.43(3H, s). preparation 29-73- ((2, 4-dichlorophenyl) hydroxymethyl5- (methoxycarbonyl) -2-methylbenzo [ b ] furan

3- (2, 4-Dichlorobenzoyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (0.84g, 2.31mmol) was dissolved in tetrahydrofuran (20ml), and a tetrahydrofuran solution (1.0M, 5ml, 5mmol) of a borane-tetrahydrofuran complex was added thereto, and the mixture was stirred at room temperature for 30 minutes and at 50 ℃ for 2 hours. The reaction mixture was concentrated under reduced pressure, and a saturated aqueous ammonium chloride solution was added to the residue to conduct extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the desired product (0.8g) as a colorless oil. The crude product was used directly in the following reaction.¹H-NMR(CDCl₃δ ppm): 8.27(1H, s), 7.92(1H, dd, J ═ 1.6 and 8.4Hz), 7.86(1H, d, J ═ 9.2Hz), 7.39(1H, d, J ═ 8.9Hz), 7.36(2H, m), 6.27(1H, d, J ═ 2.9Hz), 3.90(3H, s), 2.46(3H, s), 2.04(1H, brs), preparation 29-83- (2, 4-dichlorobenzyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan

Trifluoroacetic acid (50ml) was placed in an ice-water bath, and sodium borohydride (873mg, 23.1mmol) was slowly added over 20 minutes under nitrogen at 5-7 ℃. A solution of 3- ((2, 4-dichlorophenyl) hydroxymethyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan in methylene chloride was added dropwise thereto over 20 minutes, followed by stirring at room temperature for 45 minutes. After completion of the reaction, the reaction mixture was poured into ice water, and a 25% aqueous solution of sodium hydroxide was added to make the solution alkaline. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the filtrate was concentrated under reduced pressure, and the crystalline residue was purified by silica gel column chromatography to obtain the desired product as colorless crystals (0.58g, 72% in 2 steps).¹H-NMR(CDCl₃δ ppm): 7.98(1H, d, J ═ 1.5Hz), 7.95(1H, dd, J ═ 1.8 and 8.7Hz), 7.43(1H, d, J ═ 8.2Hz), 7.42(1H, d, J ═ 2.2Hz), 7.10(1H, dd, J ═ 2.2 and 8.3Hz), 6.96(1H, d, J ═ 8.3Hz), 4.03(2H, s), 3.89(3H, s), 2.40(3H, s), preparation 29-95-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan

A mixture of 3- (2, 4-dichlorobenzoyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (0.57, 1.6mmol), methanol (6ml), tetrahydrofuran (6ml) and a 2M aqueous solution of sodium hydroxide (8.5ml) was heated under reflux for 40 minutes. The reaction mixture was concentrated under reduced pressure, water was added to the residue, which was then made acidic with 3N hydrochloric acid, and the precipitated solid was extracted with hot ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered to remove the drying agent, and the filtrate was concentrated under reduced pressure to give the desired product (0.54g, quantitative) as colorless crystals. ¹H-NMR(DMSO-d₆δ ppm): 12.70(1H, brs), 7.88(1H, d, J ═ 1.6Hz), 7.81(1H, dd, J ═ 1.8 and 8.7Hz), 7.62(1H, d, J ═ 2.1Hz), 7.55(1H, d, J ═ 8.8Hz), 7.34(1H, dd, J ═ 2.1 and 8.3Hz), 7.25(1H, d, J ═ 8.3Hz), 4.09(2H, s), 2.44(3H, s), preparation 30-15-methylsalicylic acid ethyl ester

Concentrated sulfuric acid (1.0g) was added to a solution of 5 methylsalicylic acid (9.90g) in ethanol (100ml), and the mixture was refluxed for 21 hours. The reaction solution was concentrated to obtain an oily substance containing the objective substance as a main component.¹H-NMR(CDCl₃δ ppm): 1.40(3H, t, J ═ 7.1Hz), 2.26(3H, s), 4.38(2H, quartz, J ═ 7.1Hz), 6.86(1H, d, J ═ 8.5Hz), 7.23(1H, dd, J ═ 8.4 and 2.3Hz), 7.61(1H, d, J ═ 1.8Hz), 10.66(1H, s), preparation 30-22-acetoxy-5-methylbenzoic acid ethyl ester

To the oil, acetic acid (40ml) and acetic anhydride (40ml) were added, and the mixture was heated at 100 ℃ for 20 minutes. After concentration, ether was added, and the mixture was washed with water and a saturated aqueous solution of sodium hydrogencarbonate. After drying over magnesium sulfate, concentration gave the desired product (9.66) as a yellow oil.¹H-NMR(CDCl₃δ ppm): 1.37(3H, t, J ═ 7.2Hz), 2.33(3H, s), 2.38(3H, s), 4.33(2H, quartz, J ═ 7.4Hz), 6.98(1H, d, J ═ 8.2Hz), 7.34(1H, d, J ═ 8.6Hz), 7.82(1H, s) preparation 30-33-acetyl-5-methylsalicylic acid ethyl ester

To a solution of ethyl 2-acetoxy-5-methylbenzoate (8.50g) in 1, 2-dichloroethane (25ml) was added aluminum chloride (8.80g), and the mixture was stirred at room temperature for 30 minutesA clock. Ice was added to the reaction solution, followed by extraction with ethyl acetate. After washing with water, it was dried over magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the objective product (2.28g) as a white solid.¹H-NMR(CDCl₃δ ppm): 1.43(3H, t, J ═ 7.2Hz), 2.32(3H, s), 2.69(3H, s), 3.92(2H, quartz, J ═ 7.2Hz), 7.79(1H, s), 7.86(1H, d, J ═ 2.3Hz), 12.08(1H, s), preparation 30-42- (2, 4-dichlorobenzoyl) -7- (ethoxycarbonyl) -3, 5-dimethylbenzo [ b ] furan

Ethyl 3-acetyl-5-methylsalicylate (2.40g), 2', 4-trichloroacetophenone (2.10g), potassium iodide (1.50g) and potassium carbonate (2.76g) were placed in acetone (70ml) and stirred at room temperature for 7 hours. Acetone (about 50ml) was distilled off from the reaction mixture, water (20ml) was added, and the precipitated crystals were collected by filtration, washed with diisopropyl ether, and dried to obtain the desired product (0.80g) as a white solid.¹H-NMR(CDCl₃δ ppm): 1.20(3H, t, J ═ 7.2Hz), 2.52(3H, s), 2.65(3H, s), 4.32(2H, quartz, J ═ 7.2Hz), 7.39(1H, d, J ═ 8.4Hz), 7.50(1H, s), 7.53(1H, d, J ═ 8.3Hz), 7.67(1H, s), 7.99(1H, s), preparation 30-57-carboxy-2- (2, 4-dichlorobenzyl) -3, 5-dimethylbenzo [ b ] furan

2- (2, 4-Dichlorobenzoyl) -7- (ethoxycarbonyl) -3, 5-dimethylbenzo [ b ] furan (0.78g) and hydrazine monohydrate (0.70g) were put in ethylene glycol (6.5ml), and stirred at 140 ℃ for 2 hours. After cooling, potassium hydroxide (0.75g) was added thereto, and the mixture was stirred at 150 ℃ for 4 hours. After cooling, ice and concentrated hydrochloric acid were added, and the precipitate was collected by filtration, washed with water and diisopropyl ether, and dried to obtain the desired product (0.66g) as white crystals.¹H-NMR(DMSO-d₆δ ppm): 2.16(3H, s), 2.42(3H, s), 4.23(2H, s), 7.27(1H, d, J ═ 8.3Hz), 7.38(1H, dd, J ═ 8.3 and 2.1Hz), 7.57(2H, 2s), 7.63(1H, d.J ═ 2.1Hz), preparation 31-15- (methoxycarbonyl) -2-methylbenzo [ b ] furan

Methyl 4-hydroxybenzoate (25.51g), 2, 3-dichloropropene (22.33g) and potassium carbonate (27.65g) were placed in 2-butanone (1)50ml) was added thereto, and the mixture was heated at 70 ℃ for 20 hours. The reaction solution was concentrated, water was added thereto, and extraction was performed with toluene. The extract was washed with saturated brine and then concentrated. To the residue (34.5g) was added diethylaniline (100ml), and the mixture was stirred at 200 ℃ for 89 hours. After cooling, toluene and concentrated hydrochloric acid were added, and the toluene layer was washed with saturated brine and dried over sodium sulfate. After concentration, formic acid (80ml) was added to the residue (34.5g), and the mixture was refluxed for 25 hours. After concentration, ethyl acetate and water were added to separate a toluene layer, which was washed with a saturated aqueous sodium bicarbonate solution. After drying over magnesium sulfate, the residue was concentrated, and the residue was subjected to silica gel column chromatography to obtain the desired product (3.30 g). ¹H-NMR(CDCl₃δ ppm): 2.47(3H, s), 3.93(3H, s), 6.44(1H, s), 7.41(1H, d, J ═ 8.8Hz), 7.94(1H, dd, J ═ 8.6 and 1.7Hz), 8.20(1H, d, J ═ 1.6Hz), preparation 31-25- (methoxycarbonyl) -2-methyl-3- (4-phenylbenzoyl) benzo [ b ] furan

Aluminum chloride (0.80g) was placed in methylene chloride (10ml), and stirred at room temperature. To this was added 4-phenylbenzoyl chloride (0.67g), and a solution of 5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (0.67g) in methylene chloride (5ml) was further added, followed by stirring for additional 4 hours. Ice was added to the reaction solution, followed by extraction with ethyl acetate. The extract was washed 2 times with a saturated aqueous sodium bicarbonate solution and 1 time with a saturated brine. After drying over sodium sulfate, concentration was carried out to obtain the objective product (1.36 g).¹H-NMR(CDCl₃δ ppm): 2.58(3H, s), 3.88(3H, s), 7.39-8.28(12H, m.) preparation 31-35- (methoxycarbonyl) -2-methyl-3- (4-phenylbenzyl) benzo [ b ] furan

A1M borane-tetrahydrofuran solution (8ml) was stirred at room temperature, and a solution of 5- (methoxycarbonyl) -2-methyl-3- (4-phenylbenzoyl) benzo [ b ] furan (1.36g) in tetrahydrofuran (20ml) was added dropwise thereto over 20 minutes. Thereafter, the mixture was stirred at 50 ℃ for 50 minutes. After cooling, ethyl acetate and a 10% aqueous ammonium chloride solution were added, and the separated organic layer was dried over sodium sulfate and concentrated.

In another vessel, cooled in an ice-water bath, sodium borohydride (1.51g) was added to trifluoroacetic acid (50ml) over 10 minutes. By usingA dichloromethane (20ml) solution of the above-described concentrated residue (1.51g) was added dropwise thereto over 40 minutes. After the dropwise addition, the ice-water bath was removed, and the mixture was stirred at room temperature for 15 minutes. Ethyl acetate and a 10% aqueous sodium hydroxide solution were added to the reaction mixture, and the ethyl acetate layer was separated and washed with a 10% aqueous sodium hydroxide solution until the mixture became alkaline. After drying over sodium sulfate, concentration was carried out to obtain the objective product (1.31 g).¹H-NMR(CDCl₃δ ppm): preparation of 31-45-carboxy-2-methyl-3- (4-phenylbenzyl) benzo [ b ] furan of example 46(3H, s), 3.89(3H, s), 4.04(2H, s), 7.22-7.58(10H, m), 7.94(1H, d, J ═ 8.6Hz), 8.09(1H, s). preparation

The stream of 5- (methoxycarbonyl) -2-methyl-3- (4-phenylbenzyl) benzo [ b ] furan (1.31g) was heated back in 10% aqueous sodium hydroxide (10ml), methanol (10ml) and tetrahydrofuran (10ml) for 1 hour. After the reaction solution was concentrated, concentrated hydrochloric acid was added to adjust the reaction solution to acidity, and the precipitated solid was collected by filtration, washed with water and diisopropyl ether, and dried to obtain the desired product (0.68 g).¹H-NMR(DMSO-d₆δ ppm): 2.52(3H, s), 4.07(2H, s), 7.29-7.36(3H, m), 7.42(2H, t, J ═ 7.8Hz), 7.53-7.63(5H, m), 7.81(1H, d, J ═ 8.6Hz), 7.99(1H, s). preparation 32-12-acetyl-5-bromobenzo [ b ] furan

5-Bromosalicylaldehyde (10.05g), bromoacetone (8.0g) and potassium carbonate (13.80g) were refluxed in 2-butanone (100ml) for 1 hour. About 50ml of 2-butanone was distilled off, and ice was added. The precipitate was collected by filtration and washed with water and hexane to obtain the objective product (10.50 g).¹H-NMR(CDCl₃δ ppm): 2.62(3H, s), 7.44(1H, s), 7.47(1H, d, J ═ 8.9Hz), 7.57(1H, dd, J ═ 8.9 and 2.0Hz), 7.86(1H, d, J ═ 2.0Hz), preparation 32-25-bromo-2-ethylbenzo [ b ] furan

In ethylene glycol (60ml), 2-acetyl-5-bromobenzo [ b ] furan (10.00g) and hydrazine monohydrate (8.00g) were stirred at 150 ℃ for 2 hours. After cooling, potassium hydroxide (9.00g) was added thereto, and the mixture was stirred at 150 ℃ for 2 hours. After cooling, toluene (200ml) and water (100ml) were added to the mixture, and the separated toluene was washed with 10% aqueous ammonium chloride (100ml)And (3) a layer. After drying over magnesium sulfate, concentration was carried out to obtain the objective product (8.30 g).¹H-NMR(CDCl₃δ ppm): 1.33(3H, t, J ═ 7.5Hz), 2.79(2H, quartz., J ═ 7.5Hz), 6.32(1H, s), 7.24-7.31(2H, m), 7.59(1H, d, J ═ 1.8Hz), preparation 32-35-carboxy-2-ethylbenzo [ b ] furan

Magnesium (1.50g) was put in diethyl ether (30ml), and stirred at room temperature. 5-bromo-2-ethylbenzo [ b ] furan (8.30g), methyl iodide (0.55g) in diethyl ether (30ml) was added dropwise thereto over 30 minutes. Then, the mixture was refluxed for 50 minutes and cooled in an ice water bath. In another vessel, the pulverized dry ice was stirred in ether, and the above-prepared grignard reagent was pipetted for about 5 minutes. 2N hydrochloric acid was added to the reaction solution to adjust the reaction solution to acidity, and an ether layer was separated. The mixture was made alkaline with a 5% aqueous solution of sodium hydroxide, and the separated aqueous layer was made acidic with 2N hydrochloric acid. After extraction with diethyl ether, dried over sodium sulfate and concentrated, the desired product (2.48g) was obtained. ¹H-NMR(DMSO-d₆δ ppm): 1.26(3H, t, J ═ 7.6Hz), 2.80(2H, quartz, J ═ 7.5Hz), 6.69(1H, s), 7.56(1H, dd, J ═ 8.6Hz), 7.83(1H, dd, J ═ 8.6and 1.8Hz), 8.16(1H, d, J ═ 1.7Hz), 12.73(1H, s), preparation 32-42-ethyl-5- (methoxycarbonyl) benzo [ b ] furan

5-carboxy-2-ethylbenzo [ b ] furan (2.48g) and concentrated sulfuric acid (0.30g) were placed in methanol (50ml), and the mixture was stirred with heating at 60 ℃ for 16 hours. The reaction mixture was concentrated, chloroform was added thereto, and the mixture was washed with a saturated aqueous sodium bicarbonate solution. The chloroform layer was separated, dried over magnesium sulfate, and concentrated to obtain the objective product (2.40 g).¹H-NMR(CDCl₃δ ppm): 1.35(3H, t, J ═ 7.6Hz), 2.82(2H, quartz., J ═ 7.6Hz), 3.93(3H, s), 6.44(1H, s), 7.42(1H, dd, J ═ 8.8Hz), 7.94(1H, dd, J ═ 8.6and 1.8Hz), 8.22(1H, d, J ═ 1.6Hz), preparation 32-53- (2, 4-dichlorobenzoyl) -2-ethyl-5- (methoxycarbonyl) benzo [ b ] furan

According to the same manner as in preparation example 31-2, from 2-ethyl-5- (methoxycarbonyl) benzo [ b ] furan (2.40g), ammonium chloride (3.33g) and 2, 4-dichlorobenzoyl chloride (2.80g),the desired product (2.28g) was obtained.¹H-NMR(CDCl₃δ ppm): 1.30(3H, t, J ═ 7.6Hz), 2.79(2H, quartz, J ═ 7.5Hz), 3.91(3H, s), 7.38(1H, d, J ═ 8.2Hz), 7.42(1H, dd, J ═ 8.1 and 1.9Hz), 7.50(1H, d, J ═ 8.8Hz), 7.54(1H, d, J ═ 1.8Hz), 8.05(1H, dd, J ═ 8.6and 1.8Hz), 8.18(1H, d, J ═ 1.8Hz), preparation 32-63- (2, 4-dichlorobenzyl) -2-ethyl-5- (methoxycarbonyl) benzo [ b ] furan [ b ] (b)

The same procedures used in preparation 31-3 were repeated except for using 3- (2, 4-dichlorobenzoyl) -2-ethyl-5- (methoxycarbonyl) benzo [ b ] furan (2.28g) to give the desired product (2.20 g).¹H-NMR(CDCl₃δ ppm): 1.28(3H, t, J ═ 7.6Hz), 2.76(2H, quartz, J ═ 7.6Hz), 3.90(3H, s), 4.04(2H, s), 6.92(1H, d, J ═ 8.4Hz), 7.09(1H, dd, J ═ 8.4and 2.2Hz), 7.42-7.46(2H, m), 7.96(1H, dd, J ═ 8.6 and 1.7Hz), 7.98(1H, d, J ═ 1.5Hz), preparation 32-75-carboxy-3- (2, 4-dichlorobenzyl) -2-ethylbenzo [ b ] furan

The same procedures used in preparation 31-4 were repeated except for using 3- (2, 4-dichlorobenzyl) -2-ethyl-5- (methoxycarbonyl) benzo [ b ] furan (2.20g) to give the desired product (1.50 g).¹H-NMR(DMSO-d₆δ ppm): 1.20(3H, t, J ═ 7.5Hz), 2.81(2H, quartz, J ═ 7.5Hz), 4.11(2H, s), 7.20(1H, d, J ═ 8.4Hz), 7.34(1H, dd, J ═ 8.3 and 2.2Hz), 7.58(1H, d, J ═ 8.5Hz), 7.63(1H, d, J ═ 2.2Hz), 7.83(1H, dd, J ═ 8.6 and 1.7Hz), 7.89(1H, d, J ═ 1.6Hz), 12.78(1H, brs), preparation 33-15-bromo-2-propionylbenzo [ b ] furan

The same procedures used in preparation example 32-1 were repeated except for using 5-bromosalicylaldehyde (5.50g), 1-bromo-2-butanone (5.00g) and potassium carbonate (8.00g) to give the desired product (7.10 g). ¹H-NMR(CDCl₃δ ppm): 1.26(3H, t, J ═ 7.3Hz), 3.00(2H, quartz, J ═ 7.3Hz), 7.42(1H, s), 7.46(1H, d, J ═ 8.9Hz), 7.56(1H, dd, J ═ 8.8 and 2.0Hz), 7.84(1H, d, J ═ 2.0Hz), preparation 33-25-bromo-2-propylbenzo [ b ] furan

The same procedures used in preparation example 32-2 were repeated except for using 5-bromo-2-propionylbenzo [ b ] furan (7.00g), hydrazine monohydrate (5.00g) and potassium hydroxide (6.00g) to give the desired product (5.85 g).¹H-NMR(CDCl₃δ ppm): 1.01(3, t, J ═ 7.4Hz), 1.72-1.81(2H, m), 2.73(2H, t, J ═ 7.3Hz), 6.32(1H, s), 7.25-7.30(2H, m), 7.59(1H, d, J ═ 1.8Hz), preparation 33-35-carboxy-2-propylbenzo [ b ] furan

The same procedures used in preparation example 32-3 were repeated except for using 5-bromo-2-propylbenzo [ b ] furan (5.85g), methyl iodide (10.0g), magnesium (2.67g) and dry ice to give the desired product (3.01 g).¹H-NMR(DMSO-d₆δ ppm): 0.95(3H, t, J ═ 7.4Hz), 1.67-1.75(2H, m), 2.76(2H, t, J ═ 7.4Hz), 6.70(1H, d, J ═ 0.70Hz), 7.56(1H, d, J ═ 8.5Hz), 7.83(1H, dd, J ═ 8.6 and 1.7Hz), 8.15(1H, d, J ═ 1.5Hz), preparation 33-45- (methoxycarbonyl) -2-propylbenzo [ b ] furan

The same procedures used in preparation 32-4 were repeated except for using 3.00g of 5-carboxy-2-propylbenzo [ b ] furan to give the desired product (3.22 g). ¹H-NMR(CDCl₃δ ppm): 1.02(3H, t, J ═ 7.4Hz), 1.76-1.81(2H, m), 2.76(2H, t, J ═ 7.5Hz), 3.93(3H, s), 6.44(1H, s), 7.42(1H, dd, J ═ 8.2Hz), 7.94(1H, dd, J ═ 8.6 and 1.7Hz), 8.21(1H, s), preparation 33-53- (2, 4-dichlorobenzoyl) -5- (methoxycarbonyl) -2-propylbenzo [ b ] furan

The same procedures used in preparation 31-2 were repeated except for using 5- (methoxycarbonyl) -2-propylbenzo [ b ] furan (3.20g), aluminum chloride (4.00g) and 2, 4-dichlorobenzoyl chloride (3.84g) to give the desired product (4.29 g).¹H-NMR(CDCl₃δ ppm): 0.91(3H, t, J ═ 7.4Hz), 1.72-1.80(2H, m), 2.76(2H, t, J ═ 7.5Hz), 3.91(3H, s), 7.38(1H, d, J ═ 8.1Hz), 7.42(1H, dd, J ═ 8.2and 1.9Hz), 7.50(1H, d, J ═ 8.3Hz), 7.54(1H, d, J ═ 2.0Hz), 8.04(1H, dd, J ═ 8.7 and 1.8Hz), 8.15(1H, d, J ═ 1.9Hz), preparation 33-63- (2, 4-dichlorobenzyl) -5- (methoxycarbonyl) -2-propylbenzo [ b ] furan

The same procedures used in preparation 31-3 were repeated except for using 3- (2, 4-dichlorobenzoyl) -5- (methoxycarbonyl) -2-propylbenzo [ b ] furan (2.42g) to give the desired product (2.27 g).¹H-NMR(CDCl₃δ ppm): 0.94(3H, t, J ═ 7.4Hz), 1.69 to 1.77(2H, m), 2.71(2H, t, J ═ 7.5Hz), 3.89(3H, s), 4.04(2H, s), 6.91(1H, d, J ═ 8.4Hz), 7.08(1H, dd, J ═ 8.3 and 2.1Hz), 7.43 to 7.46(2H, m), 7.94 to 7.98(2H, m), preparation 33-75-carboxy-3- (2, 4-dichlorobenzyl) -2-propylbenzo [ b ] furan

The same procedures used in preparation 3-4 were repeated except for using 3- (2, 4-dichlorobenzyl) -5- (methoxycarbonyl) -2-propylbenzo [ b ] furan (2.25g) to give the desired product (2.04 g).¹H-NMR(DMSO-d₆δ ppm): 0.87(3H, t, J ═ 7.4Hz), 1.60-1.68(2H, m), 2.76(2H, t, J ═ 7.4Hz), 4.11(2H, s), 7.18(1H, d, J ═ 8.4Hz), 7.34(1H, dd, J ═ 8.3and 2.2Hz), 7.58(1H, d, J ═ 8.7Hz), 7.63(1H, d, J ═ 2.1Hz), 7.83(1H, dd, J ═ 8.6 and 1.7Hz), 7.89(1H, d, J ═ 1.6Hz), 12.75(1H, brs), preparative examples 34-14- ((2, 2-dimethoxy) ethoxy) benzoic acid methyl ester

Methyl 4-hydroxybenzoate (15.52), bromoacetaldehyde dimethylacetal (16.90g) and 60% sodium hydride (5.00g) were placed in dimethylformamide (50ml), and heated at 80 ℃ for 18 hours. After dimethylformamide was distilled off from the reaction solution, toluene and water were added. The toluene layer thus separated was dried over magnesium sulfate, and the solvent was distilled off to obtain the desired product (16.00 g).¹H-NMR(CDCl₃δ ppm): 3.47(6H, s), 3.89(3H, s), 4.06(1H, d, J ═ 5.3Hz), 4.73(1H, d, J ═ 5.2Hz), 6.94(2H, d, J ═ 8.9Hz), 7.99(2H, d, J ═ 8.9Hz), preparation 34-25- (methoxycarbonyl) benzo [ b ] furan

Methyl 4- ((2, 2-dimethoxy) ethoxy) benzoate (10.00g) and polyphosphoric acid (20.00g) were placed in 1, 2-dichloroethane (50ml) and refluxed for 1 hour. After cooling, ice was added and the separated organic layer was washed with 10% hydrochloric acid. After the drying with magnesium sulfate was carried out,the resulting extract was purified by column chromatography to give the desired product (0.86 g).¹H-NMR(CDCl₃δ ppm): 3.94(3H, s), 6.85(1H, dd, J ═ 2.4 and 0.8Hz), 7.53(1H, d, J ═ 8.6Hz), 7.69(1H, d, J ═ 2.2Hz), 8.03(1H, dd, J ═ 8.7 and 1.7Hz), 8.35(1H, d, J ═ 1.7Hz), preparation 34-33- (2, 4-dichlorobenzoyl) -5- (methoxycarbonyl) -2-propylbenzo [ b ] furan

The same procedures used in preparation 31-2 were repeated except for using 5- (methoxycarbonyl) benzo [ b ] furan (0.85g), aluminum chloride (1.11g) and 2, 4-dichlorobenzoyl chloride (1.00g) to give the desired product (0.34 g).¹H-NMR(CDCl₃δ ppm): 3.96(3H, s), 7.38(1H, dd, J ═ 8.3 and 1.9Hz), 7.46(1H, d, J ═ 8.2Hz), 7.50(1H, d, J ═ 2.0Hz), 7.57(1H, d, J ═ 8.9Hz), 7.94(1H, s), 8.13(1H, dd, J ═ 8.7 and 1.8Hz), 8.94(1H, d, J ═ 1.4Hz), preparation 34-43- (2, 4-dichlorobenzyl) -5- (methoxycarbonyl) benzo [ b ] furan [ b ] (1H, d, J ═ 1.4Hz)

The same procedures used in preparation 16-2 were repeated except for using 3- (2, 4-dichlorobenzoyl) -5- (methoxycarbonyl) benzo [ b ] furan (0.34g) to give the desired product (0.28 g).¹H-NMR(CDCl₃δ ppm): 3.93(3H, s), 4.11(2H, s), 7.13-7.18(2H, m), 7.41(1H, s), 7.50(1H, d, J ═ 8.8Hz), 8.03(1H, dd, J ═ 8.7 and 1.8Hz), 8.21(1H, d, J ═ 1.7Hz), preparation 34-55-carboxy-3- (2, 4-dichlorobenzyl) benzo [ b ] furan

The same procedures used in preparation example 35-5 were repeated except for using 0.28g of 3- (2, 4-dichlorobenzyl) -5- (methoxycarbonyl) benzo [ b ] furan to give the desired product (0.26 g).¹H-NMR(CDCl₃δ ppm): 4.13(2H, s), 7.17-7.18(2H, m), 7.43-7.55(2H, m), 7.54(1H, d, J ═ 8.8Hz), 8.10(1H, dd, J ═ 8.7 and 1.7Hz), 8.30(1H, d, J ═ 1.6Hz), preparation 35-15-bromo-2-methylbenzo [ b ] thiophene

4-bromobenzenethiol (10.0g, 52.8mmol) was dissolved in acetone (100ml), and anhydrous potassium carbonate (8.8g, 63mmol) and 2, 3-dichloropropene (7.0g, 63mmol) were added thereto, followed by stirring at room temperatureFor 14 hours. After acetone was distilled off under reduced pressure, toluene and water were added to the residue to separate a toluene layer. The organic layer was washed with water and dried over anhydrous sodium sulfate. After the drying agent was removed by filtration, the filtrate was concentrated under reduced pressure to give a pale yellow oil (13.9 g). This oil was dissolved in diethylaniline (45ml), and the mixture was stirred at 205 ℃ for 50 hours. After removing diethylaniline by distillation under the reduced pressure, 3N hydrochloric acid and toluene were added to the residue, and after separating the toluene layer, the organic layer was dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The crystalline oily substance of the residue was dissolved in hexane, and the insoluble oily substance was removed by decantation, followed by concentration under reduced pressure, and the residue was recrystallized from a small amount of hot hexane to obtain the desired product (5.9g, 58%) as colorless crystals. ¹H-NMR(CDCl₃δ ppm): 7.77(1H, d, J ═ 1.9Hz), 7.58(1H, d, J ═ 8.4Hz), 7.33(1H, dd, J ═ 1.98.4 Hz), 6.90(1H, s), 2.58(1H, d, J ═ 1.0Hz), preparation 35-25-carboxy-2-methylbenzo [ b ] thiophene [ b ]

Magnesium (1.93g, 79mmol) was suspended in diethyl ether, and a solution of a mixture of 5-bromo-2-methylbenzo [ b ] thiophene (3.0g, 13.2mmol) and methyl iodide (5.62g, 40mmol) in diethyl ether (50ml) was added dropwise thereto, and gentle reflux was continued. About 30 minutes was required for the dropwise addition. After completion of the dropwise addition, the mixture was refluxed for 50 minutes and then cooled with ice. Diethyl ether to which crushed dry ice was added was slowly added to the reaction solution while stirring. The reaction solution containing the oil was extracted with 2N hydrochloric acid, and the organic layer was extracted with 1M aqueous sodium hydroxide solution. The aqueous layer was made acidic with 3M hydrochloric acid, and the precipitated crystals were extracted with diethyl ether. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate. After removing the drying agent by filtration, the filtrate was concentrated under reduced pressure to give the desired product as colorless crystals (2.1g, 82%).¹H-NMR(DMSO-d₆δ ppm): 12.84(1H, brs), 8.30(1H, d, J ═ 1.3Hz), 7.96(1H, d, J ═ 8.4Hz), 7.80(1H, dd, J ═ 1.6 and 8.4Hz), 7.26(1H, s), 2.57(1H, d, J ═ 1.1Hz), preparation 35-35- (methoxycarbonyl) -2-methylbenzo [ b ] thiophene

5-carboxy-2-methylbenzo [ b ] thiophene (2.1g, 10.9mmol) was suspended in methanol (50ml)Concentrated sulfuric acid (0.4ml) was added thereto, and the mixture was refluxed for 6 hours. After cooling, a saturated aqueous sodium bicarbonate solution was added, methanol was removed by distillation under the reduced pressure, and the residue was extracted with methyl tert-butyl ether. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the desired product (2.0g, 89%) as colorless crystals.¹H-NMR(CDCl₃δ ppm): 8.35(1H, d, J ═ 1.5Hz), 7.91(1H, dd, J ═ 1.5 and 8.4Hz), 7.78(1H, d, J ═ 8.4Hz), 7.04(1H, m), 3.94(3H, s), 2.60(3H, d, J ═ 1.2Hz), preparation 35-43- (2, 4-dichlorobenzoyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] thiophene

Aluminum chloride (1.24g, 9.3mmol) was suspended in methylene chloride (10ml), and 2, 4-dichlorobenzoyl chloride (0.97g, 4.7mmol) and then 5- (methoxycarbonyl) -2-methylbenzo [ b ] thiophene (0.8g, 3.9mmol) were added thereto and the mixture was stirred at room temperature for 4 hours. The reaction solution was poured into ice water, and ethyl acetate was added thereto for extraction. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate 2 times, then with saturated brine and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the objective product (1.5g, quantitative) as pale yellow crystals. ¹H-NMR(DMSO-d₆δ ppm): 8.49(1H, d, J ═ 1.3Hz), 8.00(1H, dd, J ═ 1.4 and8.4Hz), 7.81(1H, d, J ═ 8.4Hz), 7.49(1H, d, J ═ 1.8Hz), 7.47(1H, d, J ═ 8.3Hz), 7.40(1H, dd, J ═ 1.9 and 8.3Hz), 3.90(3H, s), 2.43(3H, s), preparation 35-53- ((2, 4-dichlorophenyl) hydroxymethyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] thiophene

3- (2, 4-Dichlorobenzoyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] thiophene (600mg, 1.58mmol) was dissolved in a mixed solvent of tetrahydrofuran (10ml) and methanol (1ml), and sodium borohydride (72mg, 1.9mmol) was added under ice bath conditions, followed by stirring for 40 minutes under ice water bath conditions. Water was added to the reaction solution, followed by extraction with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the desired product as colorless crystals (580mg, 96%).¹H-NMR(CDCl₃，δppm)：8.46(1H，d，J＝1.3Hz)，7.90(1H，dd，J＝15 and8.4Hz), 7.77(1H, d, J ═ 8.4Hz), 7.70(1H, d, J ═ 8.4Hz), 7.37(1H, d, J ═ 2.1Hz), 7.29(1H, dd, J ═ 2.1 and8.4Hz), 6.44(1H, d, J ═ 2.8Hz), 3.90(3H, s), 2.52(3H, s), 2.04(1H, brs), preparation 35-63- (2, 4-dichlorobenzyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] thiophene

Trifluoroacetic acid (30ml) is placed in an ice-water bath, and sodium borohydride (537mg, 14.2mmol) is slowly dropped in the nitrogen environment at the temperature of 5-7 ℃ for 20 minutes. A solution of 3- ((2, 4-dichlorophenyl) hydroxymethyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] thiophene in methylene chloride was added dropwise thereto over 50 minutes, and the mixture was stirred at room temperature for 70 minutes. After the reaction, the reaction solution was poured into ice water, and a 25% aqueous solution of sodium hydroxide was added to neutralize trifluoroacetic acid, thereby making the solution alkaline. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the desired product (0.52g) as colorless crystals.¹H-NMR(CDCl₃δ ppm): 8.13(1H, d, J ═ 1.4Hz), 7.94(1H, dd, J ═ 1.5 and 8.3Hz), 7.83(1H, d, J ═ 8.3Hz), 7.44(1H, d, J ═ 2.2Hz), 7.01(1H, dd, J ═ 2.1 and 8.3Hz), 6.61(1H, J ═ 8.3Hz), 4.20(2H, s), 3.90(3H, s) · 2.46(3H, s). preparation 35-75-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] thiophene, example

A mixture of 3- (2, 4-dichlorobenzyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] thiophene (0.52g, 1.42mmol), methanol (5ml), tetrahydrofuran (5ml) and a 2M aqueous solution (7ml) of sodium hydroxide was heated under reflux for 1 hour. The reaction mixture was concentrated under reduced pressure, water was added to the residue, which was then acidified with 3N hydrochloric acid, and the precipitated solid was extracted with hot ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered to remove the drying agent, and the filtrate was concentrated under reduced pressure to give the desired product as colorless crystals (0.45g, 90% in 2 steps). ¹H-NMR(DMSO-d₆，δppm)：12.91((1H，brs)，8.01(1H，d，J＝8.5Hz)，8.00(1H，s)，7.82(1H，dd，J＝1.7 and 8.3Hz)，7.66(1H，d，J＝2.0Hz)，7.25(1H，dd，J＝2.1 and 8.4Hz).6.77(1H，d, J ═ 8.4Hz), 4.24(2H, s), 2.50(3H, s.) preparation 36-12-bromophenyl (n-butane-2-keto-1-yl) sulfide

2-Bromothiophenol (3.5ml), 1-bromo-2-butanone (3.1ml), and potassium carbonate (6.90g) were placed in acetone, and stirred at room temperature for 30 minutes. Water (100ml) was added to the reaction mixture, which was extracted with toluene (100ml), dried over magnesium sulfate, and concentrated to give the objective product (8.46g) as an oil¹H-NMR(CDCl₃δ ppm): 1.07(3H, t, J ═ 7.3Hz), 2.66(2H, quartz, J ═ 7.3Hz), 7.05-7.09(1H, m), 7.27-7.29(2H, m), 7.55(1H, d, J ═ 8.4Hz), preparation 36-27-bromo-3-ethylbenzo [ b ] thiophene

Polyphosphoric acid (15.0g) was added to 2-bromophenyl (n-butane-2-on-1-yl) sulfide (6.81g), and stirred at 160 ℃ for 2 hours. Ice was added to the reaction solution, followed by extraction with toluene. The extract was washed with a 10% aqueous ammonium chloride solution and a saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, and concentrated to obtain the objective product (4.43g) as an oil.¹H-NMR(CDCl₃δ ppm): 1.36(3H, t, J ═ 7.5Hz), 2.84(2H, quartz, J ═ 7.5Hz), 7.16(1H, s), 7.27(1H, t, J ═ 7.8Hz), 7.50(1H, d, J ═ 7.6Hz), 7.70(1H, d, J ═ 7.9Hz), preparation 36-37-carboxy-3-ethylbenzo [ b ] thiophene

Magnesium (2.67g) was placed in ether (15ml) and stirred at room temperature. A solution of 7-bromo-3-ethylbenzo [ b ] thiophene (4.40g) and methyl iodide (7.76g) in diethyl ether (50ml) was added dropwise thereto over 30 minutes. Then, after refluxing for 50 minutes, it was cooled with an ice water bath. In another vessel, the pulverized dry ice was stirred in ether, and the above-prepared grignard reagent was pipetted for about 5 minutes. 2N hydrochloric acid was added to the reaction solution to adjust the reaction solution to acidity, and an ether layer was separated. The mixture was made alkaline with 5% sodium hydroxide solution, the aqueous layer was separated and made acidic with 2N hydrochloric acid. Extraction with diethyl ether and drying over sodium sulfate gave the crystalline desired product (3.22 g).¹H-NMR(CDCl₃δ ppm): 1.40(3H, t, J ═ 7.3Hz), 2.91(2H, quartz, J ═ 7.5Hz), 7.25(1H, s), 7.52(1H, t, J ═ 7.6Hz), 8.02(1H, dd, J ═ 7.9 and 0.9Hz), 8.25(1H, d, J ═ 7.4Hz), preparation 36-43-ethyl-7- (meth) examplesOxycarbonyl) benzo [ b ] thiophene

7-carboxy-3-ethylbenzo [ b ] thiophene (3.20g) and concentrated sulfuric acid (0.50g) were placed in methanol (100ml), and the mixture was stirred with heating at 60 ℃ for 16 hours. The reaction mixture was concentrated, chloroform was added thereto, and the mixture was washed with a saturated aqueous sodium bicarbonate solution. The chloroform layer was separated, dried over magnesium sulfate, and concentrated to obtain the objective product (3.04 g). ¹H-NMR(CDCl₃δ ppm): 1.39(3H, t, J ═ 7.5Hz), 2.89(2H, quartz, J ═ 7.5Hz), 4.02(3H, s), 7.22(1H, s), 7.47(1H, t, J ═ 7.8Hz), 7.95(1H, dd, J ═ 7.9 and 0.9Hz), 8.12(1H, d, J ═ 7.5Hz), preparation 36-52- (2, 4-dichlorobenzoyl) -3-ethyl-7- (methoxycarbonyl) benzo [ b ] thiophene

Aluminum chloride (2.48g) was stirred in dichloromethane (10 ml). A solution of 2, 4-dichlorobenzoyl chloride (1.94g) in dichloromethane (10ml) was added dropwise thereto over 5 minutes. After stirring for 2 hours, ice was added to the reaction solution, followed by extraction with ethyl acetate. The extract was washed 2 times with a saturated aqueous solution of sodium hydrogencarbonate and 1 time with a saturated aqueous solution of ammonium chloride. After drying over sodium sulfate, concentration was carried out to obtain the objective product (3.12 g).¹H-NMR(CDCl₃δ ppm): 1.32(3H, t, J ═ 7.5Hz), 3.28(2H, quartz, J ═ 7.5Hz), 3.99(3H, s), 7.37(1H, dd, J ═ 8.3 and 2.0Hz), 7.45(1H, d, J ═ 8.2Hz), 7.49(1H, d, J ═ 1.9Hz), 7.56(1H, t, J ═ 7.9Hz), 8.16(1H, d, J ═ 8.2Hz), 8.26(1H, d, J ═ 7.4Hz), preparations 36-67-carboxy-2- (2, 4-dichlorobenzyl) -3-ethylbenzo [ b ] thiophene [ b ] (1H, d, J ═ 8.2Hz), 8.26(1H, d, J ═ 7.4Hz)

2- (2, 4-Dichlorobenzoyl) -3-ethyl-7- (methoxycarbonyl) benzo [ b ] thiophene (2.85g) and hydrazine monohydrate (3.50g) were placed in ethylene glycol (30ml), and stirred at 160 ℃ for 1 hour. After cooling, potassium hydroxide (3.30g) was added thereto, and the mixture was stirred at 160 ℃ for 2 hours. After cooling, ice and concentrated hydrochloric acid were added, and ethyl acetate was added for extraction. After drying over sodium sulfate, concentration was carried out, and the residue was purified by silica gel column chromatography to obtain the objective product (1.98g) as white crystals. ¹H-NMR(CDCl₃，δppm)：1.20(3H，t，J＝7.6Hz)，2.88(2H，quartet，J＝7.6Hz)，4.31(2H，s)，7.12(1H, d, J ═ 8.4Hz), 7.17(1H, dd, J ═ 8.4 and 2.1Hz), 7.42(1H, d, J ═ 2.1Hz), 7.50(1H, t, J ═ 7.8Hz), 7.95(1H, dd, J ═ 7.9 and 0.8Hz), 8.16(1H, dd, J ═ 7.8 and 0.8Hz), preparation of ethyl 37-13- (2, 4-dichlorobenzylamino) -4-nitrobenzoate

A mixture of 3-fluoro-4-nitrobenzoic acid (5.20g), 2, 4-dichlorobenzylamine (14.8g) and toluene (35ml) was heated under reflux for 24 hours. After returning to room temperature, water and ethyl acetate were added and stirred, and the precipitated crystals were filtered. The chloroform layer of the filtrate was separated, the solvent was distilled off, ether was added to the obtained residue, and the precipitated crystal was filtered. The crystals were combined, washed with ether and dried to give 3- (2, 4-dichlorobenzylamino) -4-nitrobenzoic acid. Sulfuric acid (2.3g) was added to the resultant, and the mixture was heated under reflux in ethanol for 6 hours. The reaction mixture was concentrated and poured into a saturated aqueous sodium bicarbonate solution. The extract was extracted with ethyl acetate, washed with saturated brine, dried, and then the solvent was distilled off, crystals were precipitated with a mixed solvent of ethyl acetate and hexane, and the crystals were filtered and dried to obtain the desired product (4.0 g).¹H-NMR(CDCl₃δ ppm): 1.38(3H, t, J ═ 7.1Hz), 4.37(2H, q, J ═ 7.1Hz), 4.66(2H, d, J ═ 5.9Hz), 7.22 to 7.32(3H, m), 7.46(1H, d, J ═ 2.0Hz), 7.48(1H, d, J ═ 1.7Hz), 8.25(1H, d, J ═ 8.8H2), 8.37(1H, brs), preparation 37-24-amino-3- (2, 4-dichlorobenzylamino) benzoic acid ethyl ester

To ethyl 3- (2, 4-dichlorobenzylamino) -4-nitrobenzoate (1.40g) were added ethanol (7ml), tetrahydrofuran (7ml) and water (28ml), and sodium hydrogen sulfite (4.50g) was added at room temperature. Stirring was carried out at 50 ℃ for 20 minutes. Chloroform and water were added for extraction, and the organic layer was washed with saturated brine, dried and concentrated to obtain a crude product (1.4g) of the objective product. This material was used directly in the following reaction. Preparation example 37-31- (2, 4-Dichlorobenzylamino) -2-hydroxy-6- (ethoxycarbonyl) benzimidazole

A solution of the crude product of ethyl 4-amino-3- (2, 4-dichlorobenzylamino) benzoate (1.4g) and tetramethoxymethane (2.60g) in acetic acid (4ml) was stirred at 60 ℃ for 5 hours.The reaction mixture was concentrated, and ethanol (10ml) and concentrated hydrochloric acid (0.5g) were added to the obtained residue, followed by heating and refluxing for 2 hours. The reaction mixture was returned to room temperature, neutralized with saturated sodium bicarbonate, and then the solvent was distilled off under reduced pressure. The precipitated gum was collected, suspended in ethanol, filtered and dried to obtain the desired product (0.400 g).¹H-NMR(DMSO-d₆δ ppm): 1.27(3H, t, J ═ 7.1Hz), 4.24(2H, q, J ═ 7.1Hz), 5.12(2H, s), 7.04(1H, d, J ═ 8.4Hz), 7.12(1H, d, J ═ 8.2Hz), 7.37(1H, dd, J ═ 2.1 and 8.4Hz), 7.51(1H, s), 7.67-7.72(2H, m), 11.37(1H, brs), preparation 37-41- (2, 4-dichlorobenzylamino) -6- (ethoxycarbonyl) -3-methyl-2-benzimidazolone

To a solution of 1- (2, 4-dichlorobenzylamino) -2-hydroxy-6- (ethoxycarbonyl) benzimidazole (0.396g) in N, N' -dimethylformamide (4ml) was added sodium hydride (0.080g, 60% suspension in oil), and the mixture was stirred at room temperature for 1 hour. Methyl iodide (0.307g) was added thereto, and the mixture was stirred for 2 hours. The precipitated crystals were filtered, washed with water, washed with ethanol, and dried to obtain the desired product (0.348 g).¹H-NMR(DMSO-d₆δ ppm): 1.28(3H, t, J ═ 7.1Hz), 3.41(3H, s), 4.25(2H, q, J ═ 7.1Hz), 5.17(2H, s), 7.05(1H, d, J ═ 8.4Hz), 7.32(1H, d, J ═ 8.3Hz), 7.36(1H, d, J ═ 8.4Hz), 7.57(1H, s), 7.69(1H, s), 7.76(1H, d, J ═ 8.3Hz), preparation 37-56-carboxy-1- (2, 4-dichlorobenzylamino) -3-methyl-2-benzimidazole

To a mixture of 1- (2, 4-dichlorobenzylamino) -6- (ethoxycarbonyl) -3-methyl-2-benzimidazolone (0.308g), ethanol (4ml), tetrahydrofuran (8ml) and water (4ml) was added 10% sodium hydroxide (0.650g), and the mixture was stirred at 60 ℃ for 2.5 hours. The reaction mixture was partially concentrated and neutralized with a saturated aqueous sodium bicarbonate solution. The precipitated crystals were collected by filtration and dried to obtain the desired product (2.076 g).¹H-NMR(DMSO-d₆δ ppm): 3.41(3H, s), 5.16(2H, s), 7.03(1H, d, J ═ 8.4Hz), 7.29(1H, d, J ═ 8.2Hz), 7.36(1H, dd, J ═ 2.1 and 8.4Hz), 7.55(1H, d, J ═ 1.4Hz), 7.69(1H, d, J ═ 2.1Hz), 7.75(1H, dd, J ═ 1.4 and 8.3Hz), preparation 38 -11- (2, 4-dichlorobenzyl) -6- (ethoxycarbonyl) benzotriazole

Ethyl 4-amino-3- (2, 4-dichlorobenzylamino) benzoate (0.89g) and concentrated sulfuric acid (1.0g) were stirred in a mixed solvent of acetic acid (20ml), water (10ml) and tetrahydrofuran (20 ml). Sodium nitrite (3.0g) was added thereto, and the mixture was stirred at room temperature for 30 minutes. After the solvent was distilled off, toluene and water were added to separate a toluene layer, and the toluene layer was washed with a saturated aqueous sodium bicarbonate solution. The toluene layer was concentrated to obtain a crude product (0.64g) of the objective product.¹H-NMR(CDCl₃δ ppm): 1.43(3H, t, J ═ 7.2Hz), 4.43(2H, quartz, J ═ 7.1Hz), 5.97(2H, s), 6.94(1H, d, J ═ 8.4Hz), 7.18(1H, dd, J ═ 8.4 and 2.1Hz), 7.48(1H, d, J ═ 2.0Hz), 8.06(1H, dd, J ═ 8.7 and 1.3Hz), 8.12(1H, dd, J ═ 8.9and 0.9Hz), 8.23(1H, d, J ═ 1.0Hz), preparation 38-26-carboxy-1- (2, 4-dichlorobenzyl) benzotriazole

1- (2, 4-Dichlorobenzyl) -6- (ethoxycarbonyl) benzotriazole (0.60g) was heated under reflux in a mixed solvent of 5% aqueous sodium hydroxide (6g) and ethanol (20g) for 0.5 hour. After cooling, concentrated hydrochloric acid (4ml) and water (10ml) were added to the reaction mixture, followed by extraction with ethyl acetate, concentration and drying to obtain a crude product (0.50g) of the objective product. ¹H-NMR(DMSO-d₆δ ppm): 6.13(2H, s), 7.24(1H, d, J ═ 8.3Hz), 7.43 to 7.46(1H, m), 7.70 to 7.72(1H, m), 7.95(1H, d, J ═ 8.8Hz), 8.14(1H, d, J ═ 8.6Hz), 8.47(1H, s), preparation 39-14-ethyl-3-nitrobenzoic acid

4-Ethylbenzoic acid (20g, 133mmol) was cooled with ice and fuming nitric acid (94%, d ═ 1.50, 50ml) was added dropwise thereto over 40 minutes. Stirring for 1.25 hours at 4-5 ℃, pouring the yellow suspension into ice water, and filtering and collecting precipitated crystals. The crystals were dissolved in ethanol and recrystallized by adding water to give the desired product as colorless crystals (24.6g, 94.8%).¹H-NMR(CDCl₃δ ppm): 8.59(1H, d, J ═ 1.6Hz), 8.24(1H, dd, J ═ 1.6 and 8.0Hz), 7.52(1H, d, J ═ 8.0Hz), 3.00(2H, quartz, J ═ 7.5Hz), 1.33(3H, t, J ═ 7.5Hz)39-23-amino-4-ethyl benzoic acid

4-Ethyl-3-nitrobenzoic acid (5.0g, 27.4mmol) was dissolved in methanol (50ml), and Pd-C catalyst (5%, 250mg) was added thereto, followed by stirring under hydrogen atmosphere from 0 ℃ to room temperature for 1 hour. After the reaction was completed, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting crystals were washed with methyl t-butyl ether/hexane and dried to obtain the objective product (3.2g, 70.6%). ¹H-NMR(DMSO-d₆δ ppm): 12.40(1H, brs), 7.21(1H, d, J ═ 1.6Hz), 7.07(1H, dd, J ═ 1.6 and 7.6Hz), 6.99(1H, d, J ═ 7.7Hz), 5.06(2H, brs), 2.45(2H, quartz, J ═ 7.4Hz), 1.11(3H, t, J ═ 7.4Hz)

To chloroform (75ml) passed through an alumina column was added boron trifluoride diethyl ether complex (3.75g, 26.4mmol), cooled to-12 ℃ and a solution of 3-amino-4-ethylbenzoic acid (2.5g, 15.1mmol) in tetrahydrofuran (25ml) was added dropwise thereto over 20 minutes. After the addition, tert-butyl nitrite (1.87g, 18.1mmol) was added, and the temperature was raised to 5 ℃. After stirring at 5 ℃ for 1.5 hours, potassium acetate (7.4g, 75.4mmol) and 18-crown-6-ether (400mg, 1.51mmol) were added and the mixture was stirred at room temperature for 40 hours. The brown reaction mixture was concentrated under reduced pressure, and ethyl acetate/acetone (7/3, 100ml) and 1N hydrochloric acid (25ml) were added to the residue, followed by stirring at room temperature for 1 hour. After adding saturated brine (25ml), insoluble matter was removed by filtration, and the filtrate was separated. The aqueous layer was extracted with ethyl acetate/acetone (7/3, 40ml), and the organic layers were combined and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting brown oil (4.3g) was dissolved in ethyl acetate, and hydrogen chloride-diethyl ether (hydrogen chloride 61 was added to diethyl ether 40ml) and diethyl ether (100ml) were added to collect the precipitated solid by filtration. The mixture was extracted with ethyl acetate/acetone (7/3, 100ml) and saturated brine (25ml), and the aqueous layer was extracted with ethyl acetate. The drying agent was removed by filtration, the filtrate was concentrated under reduced pressure, and the resulting solid was washed with diethyl ether to give the desired product as brown crystals (0.46g, 17%). ¹H-NMR(DMSO-d₆，δppm)：12.94(2H，brs)，Preparation of 39-46- (methoxycarbonyl) -3-methyl-1H-indazole (8.04 (1H, s), 7.77(1H, d, J ═ 8.3Hz), 7.62(1H, dd, J ═ 1.1 and 8.4Hz), 2.48(3H, s)

6-carboxy-3-methyl-1H-indazole (359mg, 2.11mmol) was dissolved in methanol (50ml), concentrated sulfuric acid (0.1ml) was added, and the mixture was refluxed for 22 hours. After cooling, a saturated aqueous sodium bicarbonate solution was added, and methanol was removed by distillation under the reduced pressure. The residue was extracted with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the desired product as brown crystals (340mg, 87%).¹H-NMR(CDCl₃δ ppm): preparation of 39-51- (2, 4-dichlorobenzyl) -6- (methoxycarbonyl) -3-methyl-1H-indazole (1H, s), 7.82(1H, d, J ═ 8.4Hz), 7.72(1H, d, J ═ 8.4Hz), 3.96(3H, s), 2.61(3H, s)

6- (methoxycarbonyl) -3-methyl-1H-indazole (0.40g, 2.1mmol) was dissolved in dimethylformamide (15ml), cooled with ice, added with sodium hydride (85mg, 60% suspension in oil, NaH 2.1mmol), and stirred at 0 ℃ for 30 minutes. 2, 4-Dichlorobenzyl chloride (0.45g, 2.31mmol) was added and the mixture was stirred at room temperature for 18 hours. The reaction solution was extracted with ethyl acetate/water, and the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, the filtrate was concentrated under reduced pressure, and the resulting crystalline residue was separated and purified by silica gel column chromatography (eluent: hexane/ethyl acetate 9/1) to give the desired product (0.54g, 74%) as colorless crystals. ¹H-NMR(CDCl₃δ ppm): 8.06(1H, d, J ═ 1.1Hz), 7.82(1H, dd, J ═ 1.1 and 8.4Hz), 7.72(1H, d, J ═ 8.3Hz), 7.42(1H, d, J ═ 2.0Hz), 7.08(1H, dd, J ═ 2.0 and 8.3Hz), 6.60(1H, d, J ═ 8.4Hz), 5.63(2H, s), 3.94(3H, s), 2.61(3H, s), preparation 39-66-carboxy-1- (2, 4-dichlorobenzyl) -3-methyl-1H-indazole

1- (2, 4-Dichlorobenzyl) -6- (methoxycarbonyl) -3-methyl-1H-indazole (0.2g, 0.57mmol) was suspended in ethanol (10ml), and a 1M aqueous solution (2ml) of sodium hydroxide was added thereto, followed by stirring at 90 ℃ for 40 minutes. After the raw material disappears, the ethanol is removed by reduced pressure distillationAfter the solution was acidified with 1N hydrochloric acid (3ml), the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to give the desired product (0.19g, 99%) as colorless crystals.¹H-NMR(CDCl₃δ ppm): 8.14(1H, s), 7.87(1H, dd, J ═ 1.1 and 8.4Hz), 7.76(1H, d, J ═ 8.2Hz), 7.43(1H, d, J ═ 2.1Hz), 7.10(1H, dd, J ═ 2.1 and 8.3Hz), 6.67(1H, d, J ═ 8.3Hz), 5.65(2H, s), 2.63(3H, s), preparative example 40-13-ethyl-7- (methoxycarbonyl) -2, 4- (1H, 3H) -quinazolinedione

Dimethyl 2-aminoterephthalate (4.18g), ethyl isocyanate (2.58g) and triethylamine (1.0ml) were placed in toluene (20ml) and heated at 70 ℃ for 15 hours. After concentration, methanol (50ml) and concentrated hydrochloric acid (10ml) were added thereto, and the mixture was stirred at room temperature for 5 hours. After concentration, the residue was washed with water (50ml), methanol (50ml) and dried to obtain the objective product (2.23 g).¹H-NMR(DMSO-d₆δ ppm): 1.14(3H, t, J ═ 7.1Hz), 3.88(3H, s), 3.92(2H, quartz, J ═ 7.1Hz), 7.69(1H, dd, J ═ 8.3 and 1.4Hz), 7.75(1H, d, J ═ 1.2Hz), 8.03(1H, d, J ═ 8.2Hz), 11.58(1H, br), preparation 40-21- (2, 4-dichlorobenzyl) -3-ethyl-7- (methoxycarbonyl) -2, 4(1H, 3H) -quinazolinedione

3-Ethyl-7- (methoxycarbonyl) -2, 4- (1H, 3H) -quinazolinedione (2.17g), 2, 4-dichlorobenzoyl chloride (2.05g), potassium iodide (1.45g) and potassium carbonate (5.0g) were placed in acetone (80ml) and heated under reflux for 1.5 hours. After cooling, water (50ml) was added to the reaction mixture, and the precipitate was collected by filtration, washed with water (30ml) and methyl t-butyl ether (30ml), and dried to obtain the objective product (2.60 g).¹H-NMR(DMSO-d₆δ ppm): 1.20(3H, t, J ═ 7.0Hz), 3.83(3H, s), 4.02(2H, quartz, J ═ 7.0Hz), 5.38(2H, s), 7.16(1H, d, J ═ 8.5Hz), 7.29 to 7.31(1H, m), 7.51(1H, s), 7.75(1H, d, J ═ 2.0Hz), 7.80(1H, d, J ═ 8.1Hz), 8.22(1H, d, J ═ 8.1Hz), preparation 40-37-carboxy-1- (2, 4-dichlorobenzyl) -3-ethyl-2, 4(1H, 3H) -quinazolinedione dione

1- (2) is mixed4-Dichlorobenzyl) -3-ethyl-7- (methoxycarbonyl) -2, 4(1H, 3H) -quinazolinedione (2.36g) was placed in a mixed solvent of 5% aqueous sodium hydroxide solution (10g) and methanol (30g), and heated under reflux for 1 hour. After cooling, concentrated hydrochloric acid was added to the reaction mixture, and the precipitate was collected by filtration, washed with water (100g) and toluene (20ml), and dried to obtain the desired product (2.27g) as white crystals.¹H-NMR(DMSO-d₆，δppm)：1.19(3H，t，J＝7.0Hz)，4.02(2H，quartet，J＝7.0Hz)，5.37(2H，s)，7.14(1H，d，J＝8.4Hz)，7.30(1H，dd，J＝8.4 and 2.1Hz)，7.48(1H，s)，7.75(1H，d，J＝2.1Hz)，7.78(1H，d，J＝8.0Hz)，8.20(1H，d，J＝8.1Hz).IR(Nujol)：1724，1704，1662cm^-1Mp: 238 ℃ C. preparation example 41-13- (2, 4-Dichlorophenylmethyl) -7- (methoxycarbonyl) -2, 4(1H, 3H) -quinazolinedione

Dimethyl 2-aminoterephthalate (4.18g), N' -carbonyldiimidazole (3.98g) and N-methylmorpholine (4.0ml) were placed in tetrahydrofuran (30ml), and the mixture was stirred at room temperature for 21 hours. After the reaction solution was concentrated, acetonitrile (70ml) and 2, 4-dichlorobenzylamine (5.47g) were added, and the mixture was stirred at reflux temperature for 2 hours. The precipitated solid was washed with water (50ml) and acetonitrile (50ml), and then dried to obtain the objective product (4.64 g).¹H-NMR(DMSO-d₆δ ppm): 3.90(3H, s), 5.09(2H, s), 7.15(1H, d, J ═ 8.4Hz), 7.30(1H, dd, J ═ 8.4 and 2.1Hz), 7.65(1H, d, J ═ 2.2Hz), 7.71(1H, dd, J ═ 8.3 and 1.4Hz), 7.81(1H, s), 8.06(1H, d, J ═ 8.4Hz), 11.8(1H, brs), preparation 41-23- (2, 4-dichlorobenzyl) -7- (methoxycarbonyl) -1-methyl-2, 4(1H, 3H) -quinazolinedione dione

3- (2, 4-Dichlorobenzyl) -7- (methoxycarbonyl) -2, 4- (1H, 3H) -quinazolinedione (2.30g), methyl iodide (2.13g) and potassium carbonate (2.07g) were placed in acetone (30ml), and the mixture was refluxed for 2 hours. After cooling, the reaction mixture was concentrated, and the residue was washed with water (60ml) and methyl t-butyl ether (20ml) and dried to obtain the objective product (2.25g) as white crystals.¹H-NMR(DMSO-d₆，δppm)：3.58(3H，s)，3.93(3H，s)，5.14(2H，s)，7.17(1H，d，J＝8.4Hz)，7.29(1H，dd，J8.4 and 2.0Hz), 7.65(1H, d, J-2.0 Hz), 7.84(1H, dd, J-8.2 and 1.2Hz), 7.91(1H, s), 8.18(1H, d, J-8.2 Hz), preparation 41-37-carboxy-3- (2, 4-dichlorobenzyl) -1-methyl-2, 4(1H, 3H) -quinazolinedione

3- (2, 4-Dichlorobenzyl) -7- (methoxycarbonyl) -1-methyl-2, 4(1H, 3H) -quinazolinedione (2.02g) was placed in a mixed solvent of 5% aqueous sodium hydroxide solution (10g) and methanol (30g), and heated under reflux for 1 hour. After cooling, concentrated hydrochloric acid (5.5g) was added to the reaction mixture, and the precipitate was collected by filtration, washed with water (50g) and methanol (50g), and dried to obtain the desired product (1.90g) as white crystals.¹H-NMR(DMSO-d₈，δppm)：3.58(3H，s)，5.14(2H，s)，7.16(1H，d，J＝8.5Hz)，7.29(1H，dd，J＝8.4 and 2.1Hz)，7.65(1H，d，J＝2.1Hz)，7.82(1H，d，J＝8.2Hz)，7.91(1H，s)，8.16(1H，d，J＝8.2Hz).IR(Nujol)：1712，1691，1667cm^-1Mp: 308 ℃ 310 ℃ preparation example 42-13- (2, 4-Dichlorophenylmethyl) -7- (methoxycarbonyl) -4(3H) -quinazolinone

A solution of dimethyl 2-aminoterephthalate (4.18g) and N, N' -dimethylformamide dimethyl acetal (4.77g) in dimethylformamide (20ml) was heated at 135 ℃ for 2 hours. After the reaction solution was concentrated, 5.40g of an oil was obtained. To 2.70g of this oil was added 2, 4-dichlorobenzylamine (3.52g), and the mixture was heated at 100 ℃ for 5 minutes. After cooling, the residue was washed with water (50ml) and 2-propanol (50ml), and dried to obtain the desired product (3.10g) as white crystals. ¹H-NMR(DMSO-d₆δ ppm): 3.99(3H, s), 5.26(2H, s), 7.24-7.27(2H, m), 7.42(1H, d, J ═ 8.4Hz), 7.44(1H, d, J ═ 2.2Hz), 8.12(1H, dd, J ═ 8.3 and 1.7Hz), 8.25(1H, s), 8.35(1H, d, 8.4Hz), 8.39(1H, d, 1.4Hz), preparation 42-27-carboxy-3- (2, 4-dichlorobenzyl) -4(3H) -quinazolinedione

In a mixed solvent of 5% aqueous sodium hydroxide solution (20ml) and methanol (20ml), 3- (2, 4-dichlorobenzyl) -7- (methoxycarbonyl) -4(3H) -quinazolinedione (2.00g) was heated under reflux for 1 hour. Cooling, adding concentrated hydrochloric acid into the reaction solution, filtering and collecting precipitateAfter washing with water (50g) and toluene (30ml), the reaction mixture was dried to obtain the desired product (1.50g) as white crystals.¹H-NMR(DMSO-d₆，δppm)：5.25(2H，s)，7.19(1H，d，J＝8.4Hz)，7.37(1H，dd，J＝8.4 and 2.3Hz)，7.68(1H，d，J＝2.1Hz)，8.03(1H，dd，J＝8.2 and 1.5Hz)，8.18(1H，s)，8.23(1H，d，J＝8.4Hz)，8.58(1H，s).IR(Nujol)：1724，1679，1660cm^-1Mp: 244 ℃ C. 246 ℃ C. preparation example 43-12- ((2, 4-dichlorophenyl) acetamido) dimethyl terephthalate

Dimethyl 2-aminoterephthalate (2.09g), 2, 4-dichlorophenylacetic acid (2.05g), N' -dimethylaminopyridine (1.32g) and dicyclohexylcarbodiimide (2.22g) were put in tetrahydrofuran (20ml), stirred at room temperature for 2 hours and at 80 ℃ for 4 hours. After cooling, the precipitate was removed by filtration, and the filtrate was washed with 1N hydrochloric acid. Chloroform was added to the obtained organic layer, and the mixture was washed with a saturated aqueous sodium bicarbonate solution. After drying over sodium sulfate, the solvent was distilled off, and the residue was washed with water and methanol to give the objective product (2.54g) as white crystals. ¹H-NMR(DMSO-d₆δ ppm): 3.81(3H, s), 3.86(3H, s), 3.93(2H, s), 7.45(1H, dd, J ═ 8.3 and 2.1Hz), 7.51(1H, d, J ═ 8.3Hz), 7.73(1H, dd, J ═ 8.2 and1.7Hz), 7.97(1H, d, J ═ 8.2Hz), 8.74(1H, d, 1.7Hz), 10.64(1H, s), preparation 43-22- (2, 4-dichlorobenzyl) -3-methyl-7- (methylcarbamoyl) -4(3H) -quinazolinone

In a mixed solvent of methanol (20ml) and tetrahydrofuran (20ml), dimethyl 2- ((2, 4-dichlorophenyl) acetylamino) terephthalate (0.96g) and a 40% methylamine aqueous solution (5ml) were stirred at room temperature for 1 hour. After the reaction solution was concentrated, methanol (20ml) and concentrated hydrochloric acid (5ml) were added to the residue, and the mixture was stirred at 50 ℃ for 30 minutes. The reaction solution was concentrated to obtain the desired product (0.90g) as white crystals.¹H-NMR(CDCl₃，δppm)：3.05(3H，d，J＝4.9Hz)，3.56(3H，s)，4.28(2H，s)，6.24(1H，brs)，7.12(1H，d，J＝8.4Hz)，7.22(1H，dd，J＝8.3 and 2.1Hz)，7.48(1H，d，J＝2.2Hz)，7.86(1H，dd，J＝8.2 and 1.7Hz)，7.90(1H，d，J＝1.6Hz), 8.32(1H, d, J ═ 8.4 Hz.) preparation 43-37-carboxy-2- (2, 4-dichlorobenzyl) -3-methyl-4- (3H) -quinazolinone

In a mixture of concentrated sulfuric acid (2.0g) and water (2.0g), 2- (2, 4-dichlorobenzyl) -3-methyl-7- (methylcarbamoyl) -4(3H) -quinazolinone (0.88g) was stirred at 100 ℃ for 7 hours. After the reaction solution was allowed to cool, water (5ml) was added, and the precipitate was collected by filtration, washed with methanol, and dried to obtain the desired product (0.69g) as white crystals. ¹H-NMR(DMSO-d₆，δppm)：3.58(3H，s)，4.37(2H，s)，7.37-7.44(2H，m)，7.66(1H，d，J＝2.0Hz)，7.87(1H，d，J＝1.4Hz)，7.94(1H，dd，J＝8.2 and 1.6Hz)，8.20(1H，d，J＝8.3Hz)IR(Nujol)：1719，1676cm^-1Mp: 266 ℃ C. preparation example 44-16- (ethoxycarbonyl) -3- (2, 4-dichlorobenzyl) -3, 4-dihydro-2-methylquinazolin-hydrochloride

In carbon tetrachloride (10ml), ethyl 3-methyl-4-nitrobenzoate (2.09g), N-bromosuccinimide (2.78g) and AIBN (0.12g) were heated under reflux for 12 hours. After cooling, the precipitate was removed by filtration, and the filtrate was concentrated. To the residue were added 2, 4-dichlorobenzylamine (2.76g), potassium carbonate (2.76g), and toluene (20ml), and the mixture was stirred with heating at 100 ℃ for 1.5 hours. After cooling, the mixture was washed with water, and concentrated hydrochloric acid (5ml) was added to the toluene layer. The resulting solid was collected by filtration, washed with water and toluene, and dried to give a crude purified product of ethyl 3- (2, 4-dichlorobenzylamino) methyl-4-nitrobenzoate hydrochloride (2.74 g).

To this material were added sodium hydrogen sulfite (17g), tetrahydrofuran (20ml), ethanol (20ml) and water (80ml), and the mixture was refluxed for 1 hour. After cooling, the tetrahydrofuran layer was separated and concentrated. To the residue (ethyl 4-amino-3- (2, 4-dichlorobenzylamino) methylbenzoate as a main component) were added acetic acid (20ml) and acetic anhydride (20ml), and the mixture was heated at 100 ℃ for 1 hour. After the reaction mixture was concentrated (ethyl 4-acetylamino-3- (2, 4-dichlorobenzylamino) methylbenzoate was used as a main component), methanol (20ml) and concentrated hydrochloric acid (5ml) were added thereto, and the mixture was refluxed for 1 hour. After concentration, a crude purified product (0.68g) of the objective product was obtained. Preparation example 44-26-carboxy-3- (2, 4-dichlorobenzyl) -3, 4-dihydro-2-methyl-quinazoline hydrochloride

In a mixed solvent of 10% aqueous sodium hydroxide solution (5ml) and ethanol (10ml), 6- (ethoxycarbonyl) -3- (2, 4-dichlorobenzyl) -3, 4-dihydro-2-methylquinazolin-hydrochloride (0.68g) was stirred at 60 ℃ for 1 hour. The reaction mixture was allowed to cool, concentrated hydrochloric acid (5ml) was added thereto, and the precipitate was collected by filtration, washed with toluene and 2-propanol, and dried to obtain the desired product (0.41g) as a white crystal.¹H-NMR(DMSO-d₆，δppm)：3.55(3H，s)，4.74(2H，s)，4.90(2H，s)，7.31(1H，d，J＝8.3Hz)，7.49(1H，dd，J＝8.4 and 2.2Hz)，7.64(1H，d，J＝8.4Hz)，7.71(1H，s)，7.76(1H，d，J＝2.0Hz)，7.89(1H，d，J＝8.3Hz)，12.96(1H，brs).IR(Nujol)：1718cm^-1Mp: 277 ℃ C (decomposition). Preparation example 45-12- ((2, 4-Dichlorophenylmethyl) amino) terephthalic acid dimethyl ester

In a mixed solvent of toluene (50ml) and water (30ml), dimethyl 2-aminoterephthalate (10.45g), 2, 4-dichlorobenzyl chloride (11.74g), potassium iodide (8.33g) and potassium carbonate (13.82g) were refluxed for 20 hours. After cooling, toluene (50ml) was added, and the precipitated yellow crystals were collected by filtration, washed with water and toluene, and dried to obtain the objective product (7.87 g). The mother liquor was concentrated again, and then secondary crystals (4.43g) were obtained from ethyl acetate.¹H-NMR(CDCl₃δ ppm): 3.88(3H.s), 3.90(3H, s), 7.19-7.27(4H, m), 7.42(1H, d, J ═ 2.0Hz). 799 (1H, d, J ═ 8.8Hz), 8.20-8.28(1H, m). preparation 45-22- ((N-acetyl) - (2, 4-dichlorobenzyl) amino) dimethyl terephthalate

Dimethyl 2- (2, 4-dichlorobenzyl) aminoterephthalate (12.00g), N-dimethylaniline (7.92g) and acetyl chloride (5.5ml) were placed in toluene (140ml) and heated at 50 ℃ for 15 hours. After cooling, ice and concentrated hydrochloric acid were added to adjust the mixture to acidity, and the toluene layer was separated. After separation of the toluene layer, it was washed with water and then with a saturated aqueous sodium bicarbonate solution. After drying over sodium sulfate, concentration was carried out, and the residue was crystallized from 2-propanol to obtain the objective product (8.40g) as white crystals.¹H-NMR(CDCl₃，δppm)：3.88(3H, s), 3.90(3H, s), 7.19-7.27(4H, m), 7.42(1H, d, J ═ 2.0Hz), 7.99(1H, d, J ═ 8.8Hz), 8.20-8.28(1H, m), preparation 45-32- ((N-acetyl) - (2, 4-dichlorobenzyl) amino) terephthalic acid

Dimethyl 2- ((N-acetyl) - (2, 4-dichlorobenzyl) amino) terephthalate (2.05g) and a 10% aqueous solution of sodium hydroxide (8.00g) were placed in methanol (20ml), and heated at 60 ℃ for 1 hour. After cooling, concentrated hydrochloric acid was added to adjust the solution to acidity, and the precipitated solid was collected by filtration. After washing with water (60ml), the residue was dried to obtain the desired product (1.87g) as white crystals.¹H-NMR(DMSO-d₆δ ppm): 1.73(3H, s), 4.30(1H, d, J ═ 10.30Hz), 5.28(1H, d, J ═ 10.30Hz), 7.37(1H, dd, J ═ 8.3 and 2.0Hz), 7.41(1H, d, J ═ 8.4Hz), 7.52(1H, d, J ═ 2.0Hz), 7.55(1H, s), 7.97-7.99(2H, m), preparation 45-42- ((N-acetyl) - (2, 4-dichlorobenzyl) amino) -1, 4-dicarbamoylbenzene

In tetrahydrofuran (10ml), 2- ((N-acetyl) - (2, 4-dichlorobenzyl) amino) terephthalic acid (1.80g), N' -carbonyldiimidazole (1.62g) were stirred at room temperature for 1 hour. To this was added 25% aqueous ammonia (50ml), and after stirring for 10 minutes, the mixture was concentrated. The residue was washed with water, 2-propanol and then dried to obtain the objective product (1.56g) as white crystals.¹H-NMR(DMSO-d₆δ ppm): 1.80(3H, s), 4.27(1H, d, J ═ 15.75Hz), 5.28(1H, d, J ═ 15.75Hz), 7.37(1H, dd, J ═ 8.4 and 2.1Hz), 7.44(1H, d, J ═ 8.4Hz), 7.50(1H, brs), 7.54(1H, d, J ═ 2.1Hz), 7.55(1H, d, J ═ 1.5Hz), 7.59(1H, d, J ═ 8.0Hz), 7.66(1H, brs), 7.88(1H, d, J ═ 7.9Hz), 8.01(1H, brs), 8.04(1H, brs) preparation 45-57-carbamoyl-1- (2, 4-dichlorobenzyl) -2-methylquinazolinone-4-quinazoline-4-one-quinazoline

In a mixed solvent of concentrated hydrochloric acid (10ml) and methanol (30ml), 2- ((N-acetyl) - (2, 4-dichlorobenzyl) amino) -1, 4-dicarbamoylbenzene (1.50g) was heated under reflux for 30 minutes. Concentration gave the desired product as white crystals (1.46 g).¹H-NMR(DMSO-d₆，δppm)：2.70(3H，s)，5.70(2H，s)7.16(1H, d, J ═ 8.4Hz), 7.35(1H, dd, J ═ 8.4 and 2.1Hz), 7.77(1H, brs), 7.86(1H, brs), 8.09(1H, d, J ═ 8.2Hz), 8.32(1H, d, J ═ 8.2Hz), 8.37(1H, brs). preparation 45-67-carboxy-1- (2, 4-dichlorobenzyl) -2-methyl-4 (1H) -quinazolinone

In a mixed solvent of concentrated sulfuric acid (6ml) and water (6ml), 7-carbamoyl-1- (2, 4-dichlorobenzyl) -2-methyl-4 (1H) -quinazolinone (1.40g) was heated at 100 ℃ for 1 hour. After cooling, the precipitated solid was collected by filtration, washed with water, dried and concentrated to give the desired product as white crystals (1.46 g).¹H-NMR(DMSO-d₆δ ppm): 2.54(3H, s), 5.56(2H, s), 6.94(1H, d, J ═ 8.5Hz), 7.32(1H, d, J ═ 8.5Hz), 7.74(1H, s), 7.81(1H, d, J ═ 1.9Hz), 7.96(1H, d, J ═ 8.2Hz), 8.20(1H, d, J ═ 8.2Hz), preparation 46-14-bromomethyl-3-nitrobenzoic acid methyl ester

In carbon tetrachloride (30ml), methyl 3-nitro-4-methylbenzoate (4.147g), N-bromosuccinimide (7.12g) and AIBN (0.40g) were stirred at 70 ℃ for 42 hours. After cooling, insoluble matter was removed by filtration, and the filtrate was concentrated to give an oil (7.40g) containing the desired product. Preparation 46-22- ((N-acetyl) aminomethyl) -5- ((N-acetyl) carbamoyl) -1-nitrobenzene

The crude methyl 4-bromomethyl-3-nitrobenzoate (7.40g) obtained above was stirred in a mixed solvent of 25% aqueous ammonia (140ml) and methanol (70ml) at 50 ℃ for 1 hour. After the reaction mixture was concentrated, acetic acid (50ml) and acetic anhydride (50ml) were added thereto, and the mixture was refluxed for 30 minutes. After the reaction solution was allowed to cool, a saturated aqueous sodium bicarbonate solution was added thereto, and the mixture was extracted with ethyl acetate. After drying over magnesium sulfate, concentration was performed, and the residue was washed with chloroform to obtain the objective product. ¹H-NMR(DMSO-d₆δ ppm): 1.91(3H.s), 2.34(3H, s), 4.57(2H, d, J ═ 5.9Hz), 7.63(1H, d, J ═ 8.3Hz), 8.19(1H, d, J ═ 8.2Hz), 8.48 to 8.53(2H, m), 11.26(1H, brs), preparation 46-32- ((N-acetyl) aminomethyl) -5- ((N-acetyl) carbamoyl) aniline

In a mixed solvent of tetrahydrofuran (5ml), ethanol (5ml) and water (20ml), 2- ((N-acetyl) aminomethyl) -5- ((N-acetyl) carbamoyl) -1-nitrobenzene (1.00g) and sodium hydrogensulfite (7.0g) were heated under reflux for 1 hour. After cooling, the organic layer was separated, dried over sodium sulfate and concentrated. The residue was subjected to silica gel column chromatography and purified to obtain the objective product (1.06 g). Preparation example 46-47- (Acetylcarbamoyl) -1- (2, 4-dichlorobenzyl) -1, 4-dihydro-2-methyl-quinazoline hydrochloride

In a mixed solvent of dimethylformamide (15ml) and water (10ml), 5- (acetylaminoformyl) -2- (acetylaminomethyl) aniline (1.06g), potassium carbonate (1.40g), potassium iodide (0.8g) and 2, 4-dichlorobenzoyl chloride (1.40g) were stirred at 90 ℃ for 15 hours. After the reaction solution was concentrated, water was added thereto, and the mixture was extracted with ethyl acetate. After the extract was concentrated, methanol (5ml) and concentrated hydrochloric acid (5ml) were added to the mixture, and the mixture was refluxed for 1 hour. The reaction mixture was concentrated and purified by thin layer chromatography to obtain the desired product (0.46 g). Preparation example 46-57-carboxylic acid-1- (2, 4-dichlorobenzyl) -1, 4-dihydro-2-methyl-quinazolin-1/2 sulfate

To 7- (acetylcarbamoyl) -1- (2, 4-dichlorobenzyl) -1, 4-dihydro-2-methyl-quinazolin-hydrochloride (0.46g) were added water (1.2g) and concentrated sulfuric acid (1.0g), and the mixture was heated at 70 ℃ for 90 minutes. After cooling, ice was added, and the precipitated solid was collected by filtration, washed with water and 2-propanol, and dried to obtain the desired product (0.145 g).¹H-NMR(DMSO-d₆δ ppm): 2.24(3H, s), 4.67(2H, s), 5.14(2H, s), 7.14(1H, s), 7.23(2H, t, J ═ 7.2Hz), 7.38(1H, d, J ═ 8.4Hz), 7.65(1H, d, J ═ 7.2Hz), 7.75(1H, s). preparation 47-11- (2, 4-dichlorobenzyl) -7- (ethoxycarbonyl) -3-methyl-2 (1H) -quinoxalinone

In toluene (15ml), ethyl 4-amino-3- (2, 4-dichlorophenylmethylamino) benzoate (1.90g) and methyl pyruvate (0.55ml) were refluxed for 1 hour. The reaction solution was concentrated, and the residue was washed with methanol and dried to obtain the objective product (0.50g) as yellow crystals.¹H-NMR(DMSO-d₆，δppm)：1.28(3H，t，J＝7.2Hz)，2.53(3H，s)，4.28(2H，quartet.，J＝7.1Hz)，5.49(2H，s)，6.99(1H，d，J ═ 8.6Hz), 7.27(1H, dd, J ═ 8.4 and 2.1Hz), 7.63(1H, s), 7.76(1H, d, J ═ 2.1Hz), 7.84-7.91(1H, m), preparation 47-27-carboxy-1- (2, 4-dichlorobenzyl) -3-methyl-2 (1H) -quinoxalinone

In a mixed solvent of 5% aqueous sodium hydroxide solution (3g) and methanol (20ml), 1- (2, 4-dichlorobenzyl) -7- (ethoxycarbonyl) -3-methyl-2 (1H) -quinoxalinone (0.50g) was heated under reflux for 1 hour. After cooling, concentrated hydrochloric acid (4ml) and water (10ml) were added to the reaction mixture, and the precipitate was collected by filtration, washed with water (30g), and dried to obtain the desired product (0.36g) as yellow crystals. ¹H-NMR(DMSO-d₆δ ppm): 2.52(3H, s), 5.47(2H, s), 6.92(1H, d, J. sub.8.4 Hz), 7.26(1H, dd, J. sub.8.4 and 2.0Hz), 7.62(1H, s), 7.76(1H, d, J. sub.2.0 Hz), 7.84-7.89(1H, m). preparation 48-11- (2, 4-dichlorobenzyl) -7- (ethoxycarbonyl) -2, 3(1H, 4H) -quinoxalinedione

Oxalyl chloride (0.51ml) was added to a toluene solution of ethyl 4-amino-3- (2, 4-dichlorobenzylamino) benzoate (1.53g) and dimethylaniline (0.71 g). After stirring at room temperature for 1.5 hours, ice was added to the reaction solution. The toluene layer was separated and washed with 6N hydrochloric acid. The toluene layer was concentrated, and the residue was washed with methyl t-butyl ether and dried to obtain the objective product (1.03g) as white crystals.¹H-NMR(DMSO-d₆δ ppm): 1.24(3H, t, J ═ 7.2Hz), 4.21(2H, quartz., J ═ 7.1Hz), 5.34(2H, s), 7.24 to 7.32(3H, m), 7.30(1H, d, J ═ 2.1Hz), 7.73(1H, dd, J ═ 8.3 and 1.7Hz), 7.75(1H, d, J ═ 2.1Hz), 12.38(1H, brs), preparation 48-21- (2, 4-dichlorobenzyl) -7- (ethoxycarbonyl) -4-methyl-2, 3(1H, 4H) -quinoxalinedione

In acetone (20ml), 1- (2, 4-dichlorobenzyl) -7- (ethoxycarbonyl) quinoxaline-2, 3-dione (0.90g), methyl iodide (0.49g), and potassium carbonate (0.63g) were heated under reflux for 2 hours. After cooling, the reaction mixture was concentrated, and the residue was washed with water (150ml) and methyl t-butyl ether (100ml) and dried to obtain the desired product (0.84g) as white crystals. ¹H-NMR(DMSO-d₆，δppm)：1.25(3H，t，J＝7.1Hz)，359(3H, s), 4.23(2H, quartz, J ═ 7.1Hz), 5.37(2H, s), 7.24(1H, d, 8.5Hz), 7.30(1H, dd, J ═ 8.5 and 2.1Hz), 7.42(1H, d, J ═ 1.6Hz), 7.56(1H, d, J ═ 8.6Hz), 7.76(1H, d, J ═ 2.1Hz), 7.80(1H, dd, J ═ 8.6 and 1.6Hz), preparation 48-37-carboxy-1- (2, 4-dichlorobenzyl) -4-methyl-2, 3(1H, 4H) -quinoxalinedione-dione

In a mixed solvent of 3% aqueous sodium hydroxide solution (10g) and methanol (15g), 1- (2, 4-dichlorobenzyl) -7- (ethoxycarbonyl) -4-methyl-2, 4(1H, 4H) -quinoxalinedione (0.80g) was heated under reflux for 1 hour. After separation, concentrated hydrochloric acid (4ml) and water (10ml) were added to the reaction mixture, and the precipitate was collected by filtration, washed with water (50g) and methyl t-butyl ether (30ml), and dried to obtain the desired product (0.56g) as yellow crystals.¹H-NMR(DMSO-d₆，δppm)：3.59(3H，s)，5.35(2H，s)，7.20(1H，d，J＝8.5Hz)，7.29(1H，dd，J＝8.5 and 2.2Hz)，7.41(1H，d，J＝1.6Hz)，7.54(1H，d，J＝8.7Hz)，7.76(1H，d，J＝2.2Hz)，7.80(1H，dd，J＝8.6 and 1.7Hz).IR(Nujol)：1716，1681，1659cm^-1Mp: 320 ℃ C. preparation example 49-14- (2, 4-Dichlorophenylmethyl) -3- (ethoxycarbonyl) -5-ethylimidazo [ 1, 2-b ] pyrazole

Sodium hydride (60% oil, 0.100g) was added to a solution of ethyl 3- (ethoxycarbonyl) -5-ethylimidazole [ 1, 2-b ] pyrazole (0.348g) in N, N-dimethylformamide obtained by the method disclosed in Japanese patent application laid-open No. 5-163267, and the mixture was stirred at room temperature for 30 minutes. 2, 4-Dichlorophenylmethyl chloride (0.870g) was added to the reaction mixture, and the mixture was stirred at room temperature for 6 hours. The reaction solution was concentrated and dried to solidify, the obtained residue was dissolved in ethyl acetate, and the organic layer was washed with water and dried. The solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (eluent: chloroform/ethyl acetate 2/1) to obtain the objective product (0.510 g). ¹H-NMR(CDCl₃δ ppm): 1.19-1.25(6H, m), 2.45(2H, q), 4.18(2H, q, J ═ 7.1Hz), 5.73(2H, s), 6.57(1H, d, J ═ 8.4Hz), 7.12(1H, dd, J ═ 8.4 and 2.0Hz), 7.18(1H, s), 7.41(1H, d, J ═ 2.0Hz), 8.02(1H, s), preparation 49-23-carboxyYl-4- (2, 4-dichlorobenzyl) -5-ethylimidazol [ 1, 2-b ] pyrazole

From 4- (2, 4-dichlorobenzyl) -3- (ethoxycarbonyl) -5-ethylimidazole [ 1, 2-b ] pyrazole (0.510g), the expected product (0.445g) was obtained.¹H-NMR(DMSO-d₆δ ppm): 1.13(3H, dt, J ═ 7.3 and 1.7Hz), 2.45(2H, q, J ═ 7.3Hz), 5.75(2H, s), 6.50(1H, d, J ═ 8.3Hz), 7.34(1H, d, J ═ 8.4Hz), 7.66(2H, d, J ═ 8.8Hz), 7.83(1H, s), 11.82(1H, brs), preparation 50-15- (4-fluorophenylamino) methylene-2, 2-dimethyl-1, 3-dioxane-4, 6-dione

A mixture of p-aminobenzonitrile (2.00g), Meldrum's acid (2.56g), ethyl orthoformate (2.76g) and ethanol (10ml) was heated at a bath temperature of 120 ℃ to distill off the ethanol. To the orange solid obtained was added ethyl acetate, and after pulverization, the mixture was filtered and washed with ethyl acetate to obtain the objective product (3.28g) as a white powder.¹H-NMR(CDCl₃): 1.77(6H, s), 7.34(2H, d, J ═ 8Hz), 7.73(2H, d, J ═ 8Hz), 8.67(1H, d, J ═ 15Hz), 11.24(1H, br)

A mixture of biphenyl (10ml) and diphenyl ether (30ml) was heated to 250 ℃ and 5- (4-cyanophenylamino) methylene-2, 2-dimethyl-1, 3-dioxane-4, 6-dione (3.28g) was added, and this was stirred for 1 hour. The reaction mixture was cooled to 80 ℃ while stirring, and hexane (100ml) was added and stirred in an ice-water bath for 0.5 hour. The resulting solid was collected by filtration and washed with hexane to give a tan-colored aimed product (1.86 g).¹H-NMR(DMSO-d₆): 6.15(1H, d, J ═ 7Hz), 7.67(1H, d, J ═ 8Hz), 7.96-8.04(2H, m), 8.42(1H, d, J ═ 4Hz)

Under the condition of ice bath, phosphorus oxychloride (0.518ml) is added into DMF (9ml) with the internal temperature of 5-7 ℃ while stirring, and the mixture is stirred for 0.5 hour at room temperature. Under ice-water bath conditions, 4-hydroxy-6-quinolinecarbonitrile (860mg) was added with stirring, and stirred at the same temperature for 1 hour. 1N aqueous sodium hydroxide (18ml) was added thereto, and the mixture was stirred at room temperatureAfter stirring for 10 min, filtration and washing with water gave a light brown powder. This was purified by silica gel column chromatography (chloroform-methanol as eluent 50/1) to give the desired product (800mg) as a pale yellow powder.¹H-NMR(CDCl₃): 7.62(1H, d, J ═ 7Hz), 7.93(1H, d, J ═ 8Hz), 8.23(1H, d, J ═ 8Hz), 8.65(1H, d, J ═ 4Hz), 8.92(1H, d, J ═ 7Hz), preparation 50-44-methoxy 6-quinolinecarboxylic acid methyl ester

Concentrated sulfuric acid (5ml) was slowly added dropwise to a suspension of 4-chloro-6-quinolinecarbonitrile (910mg) in methanol (50ml) under ice-water bath conditions with stirring. After the mixture was heated under reflux for 15 hours, concentrated sulfuric acid (10ml) was added thereto, and the mixture was heated under reflux for another 24 hours. An aqueous sodium hydrogencarbonate solution was added thereto under ice-water bath conditions, and the mixture was made alkaline and extracted with chloroform 1 time. The organic layer was washed with water and saturated brine 1 time, dried over magnesium sulfate, and then concentrated under reduced pressure to dry and solidify, thereby obtaining a white solid. This was pulverized by IPE to give the desired product (910mg) as a white powder.¹H-NMR(CDCl₃): 3.98(3H, s), 4.08(3H, s), 6.80(1H, d, J ═ 7Hz), 8.05(1H, d, J ═ 8Hz), 8.29(1H, d, J ═ 8Hz), 8.83(1H, d, J ═ 7Hz), 8.97(1H, d, J ═ 4Hz), preparation of methyl 50-54-bromo-6-quinolinecarboxylate

To a solution of methyl 4-methoxy-6-quinolinecarboxylate (910mg) in DMF (7ml) was added phosphorus tribromide (1.57ml) with stirring in an ice bath. DMF (7ml) was added thereto and the mixture was heated at 80 ℃ for 3 hours. Water (50ml) was added to the reaction solution, which was then made weakly alkaline with a 1N aqueous solution of sodium hydroxide, and the resulting precipitate was collected by filtration. This was purified by silica gel column chromatography (chloroform-methanol as eluent 100/0-100/1) to give the desired product (420mg) as a yellow powder. ¹H-NMR(CDCl₃): 4.03(s, 3H), 7.78(1H, d, J ═ 7Hz), 8.15(1H, d, J ═ 8Hz), 8.36(1H, d, J ═ 8Hz), 8.77(1H, d, J ═ 7Hz), 8.95(1H, d, J ═ 4Hz), preparation 50-64- (4-phenylphenoxy) -6-quinolinecarboxylic acid

60% sodium hydroxide (38mg) was suspended in dimethylimidazolone (1ml), and 4-phenylphenol (160mg) was added thereto while stirring in a water bath, followed by stirring for 0.5 hour.Methyl 4-bromo-6-quinolinecarboxylate (100mg) was added to the mixture in a water bath, and the mixture was stirred at 100 ℃ for 5 hours and then at 140 ℃ for 3 hours. Water (10ml) was added to the reaction solution, which was then extracted with ethyl acetate 1 time. The aqueous phase was adjusted to pH4 with 1N hydrochloric acid, and the resultant solid was collected by filtration to give the objective product (73mg) as a pale brown powder.¹H-NMR(DMSO-d₆): 6.78(1H, d, J ═ 7Hz), 7.37 to 7.53(5H, m), 7.72(2H, d, J ═ 8Hz), 7.84(2H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz), 8.29(1H, d, J ═ 8Hz), 8.82(1H, d, J ═ 7Hz), 8.97(1H, s). preparation example 50-74-bromo-6-quinolinecarboxylic acid

Methyl 4-bromo-6-quinolinecarboxylate (6.00g) was dissolved in methanol (60ml) and tetrahydrofuran (40ml), and a 1N aqueous sodium hydroxide solution (30ml) was added thereto while stirring at room temperature, and after stirring for 3 hours, a 1N aqueous sodium hydroxide solution (20ml) was further added thereto, and the mixture was refluxed for 2 hours. After adjusting to pH4 by the addition of 1N hydrochloric acid, the resulting solid was collected by filtration and washed with water and diethyl ether to give 4-bromo-6-quinolinecarboxylic acid (4.65g) as a white powder. ¹H-NMR(DMSO-d₆): 8.06(1H, d, J ═ 7Hz), 8.18(1H, d, J ═ 8Hz), 8.30(1H, d, J ═ 8Hz), 8.77(1H, s), 8.83(1H, d, J ═ 7Hz)

According to the same method as in preparation example 50-6, from 4-bromo-6-quinolinecarboxylic acid (731mg), the objective product (1.04g) was obtained in white.¹H-NMR(DMSO-d₈): 5.49(2H, s), 7.26(1H, d, J ═ 7Hz), 7.35-7.51(3H, m), 7.64-7.79(6H, m), 8.04(1H, d, J ═ 8Hz), 8.21(1H, d, J ═ 8Hz), 8.80(1H, s), 8.86(1H, d, J ═ 7Hz), preparation 51-13- (4-phenylbenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same manner as in preparation example 1-1, methyl 2-methylbenzo [ b ] thiophene-5-carboxylate (200mg) was used to obtain the desired product (263mg) as pale yellow crystals.¹H-NMR(CDCl₃): 2.52(3H, s), 3.87(3H, s), 7.39-7.51(3H, m), 7.63-7.72(4H, m), 7.84(1H, d, J ═ 8Hz), 7.92-7.97(2H, m), 8.00(1H, dd, J ═ 2, 8Hz), 8.30(1H, s) preparation 51-23- ((4-phenylphenyl) methyl) -2-Methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same method as in preparation example 1-2, methyl 3- (4-phenylbenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (240mg) was used to obtain the desired product (177mg) as white crystals. ¹H-NMR(CDCl₃): 2.55(3H, s), 3.90(3H, s), 4.23(2H, s), 7.20-7.24(2H, m), 7.28-7.57(7H, m), 7.80(1H, d, J ═ 8Hz), 7.92(1H, dd, J ═ 2, 8Hz), 8.30(1H, s) preparation 51-33- ((4-phenylphenyl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- ((4-phenylphenyl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (153mg) was used to obtain the desired product (134mg) as pale yellow crystals.¹H-NMR(DMSO-d₆): 2.59(3H, s), 4.23(2H, s), 7.23-7.34(3H, m), 7.42(2H, t, J ═ 7Hz), 7.52-7.61(4H, m), 7.83(1H, d, J ═ 8Hz), 7.92(1H, d, J ═ 8Hz), 8.20(1H, s) preparation 52-13- (2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same manner as in preparation example 16-2, methyl 2-methylbenzo [ b ] thiophene-5-carboxylate (200mg) was used to give a pale yellow desired product (220 mg).¹H-NMR(CDCl₃): 2.40(3H, s), 3.89(3H, s), 7.38-7.52(4H, m), 7.80(1H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz), 8.52(1H, s) preparation 52-23- ((2-chlorophenyl) hydroxymethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester

According to the same method as in preparation example 35-5, methyl 3- (2-chlorobenzoyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (207mg) was used to give the desired product (189mg) as pale yellow crystals. ¹H-NMR(CDCl₃): preparation of 52-33- (2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester in example 52.52 (3H, s), 3.89(3H, s), 6.51(1H, s), 7.20-7.38(3H, m), 7.68(1H, dd, J ═ 2,8Hz), 7.76(1H, dd, J ═ 2,8Hz), 7.90(1H, s), 8.51(1H, s)

By the same method as in preparation examples 35-6 from 3- ((2-chlorophenyl) hydroxymethyl) -2-methylbenzo [ b ] thiopheneMethyl-5-carboxylate (170mg) gave the desired product as white crystals (162 mg).¹H-NMR(CDCl₃): 2.47(3H, s), 3.89(3H, s), 4.26(2H, s), 6.69(1H, d, J ═ 7Hz), 7.02(1H, t, J ═ 7Hz), 7.13(1H, t, J ═ 7Hz), 7.42(1H, d, J ═ 7Hz), 7.82(1H, d, J ═ 8Hz), 7.93(1H, d, J ═ 8Hz), 8.17(1H, s) preparative examples 52-43- (2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- (2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (145mg) was used to obtain the desired product (137mg) as white crystals.¹H-NMR(DMSO-d₆): 2.52(3H, s), 4.27(2H, s), 6.80(1H, d, J ═ 7Hz), 7.17(1H, t, J ═ 7Hz), 7.23(1H, t, J ═ 7Hz), 7.51(1H, d, J ═ 8Hz), 7.83(1H, dd, J ═ 2,8Hz), 8.02(1H, d, J ═ 8Hz), 8.04(1H, s) preparation 53-13-nitro-4-propylbenzoic acid

The same procedures used in preparation example 39-1 were repeated except for using 4-propylbenzoic acid (25.0g) and fuming nitric acid (60ml) to give the desired product as white crystals (31.0 g).¹H-NMR(CDCl₃δ ppm): 1.02(3H, t, J ═ 7.4Hz), 1.67-1.76(2H, m), 2.94(2H, t, J ═ 7.8Hz), 7.49(1H, d, J ═ 8.0Hz), 8.22(1H, dd, J ═ 8.0 and 1.7Hz), 8.59(1H, d, J ═ 1.8Hz), preparation 53-23-amino-4-propylbenzoic acid methyl ester

Sulfuric acid (1.0g) and methanol (300ml) were added to 3-nitro-4-propylbenzoic acid (31.0g), and the mixture was refluxed for 24 hours. After cooling, 5% Pd-C (0.60g) was added to the reaction mixture, and the mixture was stirred under a hydrogen atmosphere (normal pressure) for 6 hours. The reaction solution was filtered through celite, concentrated, and a saturated aqueous sodium bicarbonate solution was added to the residue to conduct extraction with toluene. The toluene layer was dried over sodium sulfate and concentrated to obtain the objective product (28.7g) as a brown oil.¹H-NMR(CDCl₃δ ppm): 1.00(3H, t, J ═ 7.4Hz), 1.62-1.71(2H, m), 2.50(2H, t, J ═ 7.7Hz), 3.72(2H, brs), 3.88(3H, s), 7.09(1H, d, J ═ 7.8Hz), 7.34(1H, d, J ═ 1.7Hz), 7.39(1H, dd, J ═ 7.8 and 1.7Hz), preparation 53-33-ethyl-6- (methoxycarbonyl) -1H-indazole

A solution of sodium nitrite (2.07g) in water (5ml) was added dropwise over 5 minutes to a solution of methyl 3-amino-4-propylbenzoate (5.07g) in acetic acid (150 ml). After stirring for 20 minutes, it was concentrated, and toluene and a saturated aqueous sodium hydrogencarbonate solution were added to the residue. The toluene layer separated was dried over sodium sulfate and concentrated. The residue was left to partially cure. The solid was washed with hexane and then dried to obtain the objective product (2.44g) as a brown solid. ¹H-NMR(CDCl₃δ ppm): 1.43(3H, t, J ═ 7.6Hz), 3.04(2H, quartz, J ═ 7.6Hz), 3.97(3H, s), 7.75(1H, dd, J ═ 8.4 and 0.8Hz), 7.81(1H, dd, J ═ 8.4 and 1.3Hz), 8.19(1H, d, J ═ 0.9Hz), preparation 53-41- (2, 4-dichlorobenzyl) -3-ethyl-6- (methoxycarbonyl) -1H-indazole

According to the same manner as in preparation example 39-5, from 3-ethyl-6- (methoxycarbonyl) -1H-indazole (1.84g), 60% sodium hydride (0.36g) and 2, 4-dichlorobenzyl chloride, a crude purified product (3.73g) of the objective product was obtained. This material was used in the following step without purification.¹H-NMR(CDCl₃δ ppm): 1.42(3H, t, J ═ 7.6Hz), 3.04(2H, quartz, J ═ 7.6Hz), 3.94(3H, s), 5.65(2H, s), 6.56(1H, d, J ═ 8.4Hz), 7.07(1H, dd, J ═ 8.4 and 2.0Hz), 7.43(1H, d, J ═ 2.1Hz), 7.76(1H, d, J ═ 8.4Hz), 7.81(1H, dd, J ═ 8.4 and 1.0Hz), 8.05(1H, d, J ═ 1.0Hz), preparation 53-56-carboxy-1- (2, 4-dichlorobenzyl) -3-ethyl-1H-indazole

According to the same manner as in preparation example 39-6, from unrefined 1- (2, 4-dichlorobenzyl) -3-ethyl-6- (methoxycarbonyl) -1H-indazole (3.70g), the objective product (2.10g) was obtained as brown crystals.¹H-NMR(DMSO-d₆δ ppm): 1.29(3H, t, J ═ 7.6Hz), 2.94(2H, quartz, J ═ 7.5Hz), 5.73(2H, s), 6.77(1H, d, J ═ 8.4Hz), 7.33(1H, dd, J ═ 8.4 and 2.0Hz), 7.65-7.69(2H, m), 7.87(1H, d, J ═ 8.4Hz), 8.23(1H, s), preparation 54-16-carbamoyl-3- (2, 4-dichlorobenzyl) -2-methylimidazo [ 1, 2-a ] pyridine

In dimethylformamide (5ml), 3-bromo-4- (2, 4-dichlorophenyl) -2-butanone (2.14g), synthesized according to the description of GB205177A, and 6-aminonicotinamide (2.10g) were stirred at 100 ℃ for 64 hours. After the reaction solution was concentrated, the residue was washed with water and toluene, and dried to obtain a crude product (2.00g) as a brown solid. This material was used in the following procedure without purification. Preparation 54-26-carboxy-3- (2, 4-dichlorobenzyl) -2-methylimidazo [ 1, 2-a ] pyridine

A crude purified 6-carbamoyl-3- (2, 4-dichlorobenzyl) -2-methylimidazo [ 1, 2-a ] pyridine (2.00g) was stirred in concentrated sulfuric acid (8.0g) and water (8.0g) at 100 ℃ for 1 hour. After the reaction solution was cooled, ice was added, and the precipitate was collected by filtration, washed with water, and dried to obtain a crude purified product (1.50g) as a brown solid. This material was used in the following step without purification.¹H-NMR(DMSO-d₆δ ppm): 2.31(3H, s), 4.45(2H, s), 6.88(1H, d, J ═ 8.4Hz), 7.30(1H, dd, J ═ 8.3 and 2.1Hz), 7.56(1H, d, J ═ 8.8Hz), 7.61-7.66(1H, m), 7.67(1H, d, J ═ 2.2Hz), 8.63(1H, s), preparation 552-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

The same procedures used in preparation 26-2 were repeated except for using 5-bromo-2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1.06g) to give the desired product (330mg) as white crystals.¹H-NMR(CDCl₃): preparation of methyl 56-13- (2, 3-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.80 (3H, s), 4.03(3H, s), 8.07(2H, d, J ═ 8Hz)

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate, the desired product (70mg) was obtained as white crystals.¹H-NMR(CDCl₃): 2.62(3H, s), 4.00(3H, s), 5.72(2H, s), 6.50(1H, d, J ═ 8Hz), 7.07(1H, t, J ═ 8Hz), 7.43(1H, d, J ═ 8Hz), 8.17(2H, q, J ═ 8Hz), preparation 56-23- ((3-chlorobenzo [ b ] thiophen-2-ylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to and preparation ofThe same procedures used in example 14-2 were repeated except for using methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (106mg) to give the desired product (111mg) as white crystals.¹H-NMR(CDCl₃): 2.68(3H, s), 4.03(3H, s), 5.88(2H, s), 7.35-7.48(2H, m), 7.68(1H, d, J ═ 8Hz), 7.83(1H, d, J ═ 8Hz), 8.04(1H, d, J ═ 8Hz), 8.16(1H, d, J ═ 8Hz), preparation 57-13- (2, 3-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same method as in preparation example 4-7, methyl 3- (2, 3-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (63mg) was used to obtain the desired product as white crystals (55 mg).¹H-NMR(DMSO-d₈): 2.52(3H, s), 5.65(2H, s), 6.46(1H, d, J ═ 8Hz), 7.25(1H, t, J ═ 8Hz), 7.63(1H, d, J ═ 8Hz), 8.02(1H, d, J ═ 8Hz), 8.16(1H, d, J ═ 8Hz), preparation 57-23- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (95mg) was used to obtain the desired product (82mg) as white crystals.¹H-NMR(DMSO-d₆): example 58-13- ((2-chloro-4-phenylphenyl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid methyl ester, 2.65(3H, s), 5.90(2H, s), 7.42-7.55(2H, m), 7.81(1H, d, J ═ 8Hz), 7.93(1H, d, J ═ 8Hz), 8.02(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz)

From methyl 3- (4-bromo-2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (484mg) was obtained the desired product (288mg) as white crystals. Preparation 58-23- ((2-chloro-4-phenylphenyl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid

According to the same manner as in preparation example 4-7, from methyl 3- ((3-chloro-4-phenylphenyl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylate (273mg), the desired compound (237mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：2.55(3H，s)，4.31(2H，s)，6.84(1H，d，J＝8Hz)，7.32-7.48(4H，m)，7.62-7.66(2H, m), 7.81(1H, s), 7.83(1H, d, J ═ 8Hz), 8.04(1H, d, J ═ 8Hz), 8.08(1H, s), preparation 593-chlorobenzo [ b ] thiophene-2-methylene chloride

According to the same manner as in preparation example 14-1, from 3-chlorobenzo [ b ] thiophene-2-methanol (200mg), the desired product was obtained as white crystals (220 mg).¹H-NMR(CDCl₃): 4.92(2H, s), 7.39-7.50(2H, m), 7.78-7.83(2H, m.) preparation 60-11- (2-chloro-4-phenylbenzyl) -6- (methoxycarbonyl) -3-methyl-1H-indazole

According to the same manner as in preparation example 39-5, from 6- (methoxycarbonyl) -3-methyl-1H-indazole (0.475g), 60% sodium hydroxide (0.10g) and 2-chloro-4-phenylbenzyl bromide (0.70g), a crude purified product (1.10g) of the objective product was obtained. This material was used in the following step without purification.¹H-NMR(CDCl₃δ ppm): 2.64(3H, s), 3.94(3H, s), 5.73(2H, s), 6.74(1H, d, J ═ 8.1Hz), 7.31(1H, dd, J ═ 8.1 and 1.8Hz), 7.33 to 7.38(1H, m), 7.42(2H, t, J ═ 7.5Hz), 7.50 to 7.53(2H, m), 7.64 to 7.67(2H, m), 7.74(1H, d, J ═ 8.4Hz), 7.82(1H, dd, J ═ 8.4 and 1.3Hz), 8.13(1H, s) preparation 60-26-carboxy-1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole

The desired product (0.85g) was obtained from 1- (2-chloro-4-phenylbenzyl) -6- (methoxycarbonyl) -3-methyl-1H-indazole (1.10g) according to the same method as in preparation examples 39 to 6.¹H-NMR(DMSO-d₆δ ppm): 2.67(3H, s), 5.77(2H, s), 6.91(1H, d, J ═ 8.1Hz), 7.37(1H, t, J ═ 7.3Hz), 7.44(2H, t, J ═ 7.5Hz), 7.54(1H, dd, J ═ 8.2 and 1.7Hz), 7.65(2H, d, J ═ 7.5Hz), 7.67-7.71(1H, m), 7.77(1H, d, J ═ 1.7Hz), 7.84(1H, d, J ═ 8.4Hz), 8.28(1H, s). preparative example 61-11- (4-bromo-2-chlorophenylmethyl) -6- (methoxycarbonyl) -3-methyl-1H-indazole

According to the same manner as in preparation example 39-5, from 6- (methoxycarbonyl) -3-methyl-1H-indazole (0.63g), 60% sodium hydride (0.13g) and 4-bromo-2-chlorophenylmethyl chloride (1.30g), a crude purified product (2.00g) of the objective product was obtained. This material was used in the following step without purification. Preparation example 61-21- (4-bromo-2-chlorophenylmethyl) -6-carboxy-3-methyl-1H-indazole

The desired product (1.00g) was obtained from unrefined 1- (4-bromo-2-chlorophenylmethyl) -6- (methoxycarbonyl) -3-methyl-1H-indazole (2.00g) according to the same method as in preparation example 39-6.¹H-NMR(DMSO-d₆δ ppm): 2.50(3H, s), 5.70(2H, s), 6.77(1H, d, J ═ 8.4Hz), 7.46(1H, dd, J ═ 8.3 and 2.0Hz), 7.68(1H, dd, J ═ 8.4 and 1.0Hz), 7.77(1H, d, J ═ 2.0Hz), 7.82(1H, d, J ═ 8.5Hz), 8.24(1H, s), preparation 62-13- (4-bromo-2-chlorobenzoyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan

The same procedures used in preparation 31-2 were repeated except for using 5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (1.90g), 4-bromo-2-chlorobenzoyl chloride (2.80g) and aluminum chloride (2.67g) to give the desired product (3.09g) as pale yellow crystals.¹H-NMR(CDCl₃δ ppm): 2.43(3H, s), 3.924(3H, s), 7.31(1H, d, J ═ 8.2Hz), 7.49(1H, d, J ═ 8.6Hz), 7.59(1H, d, J ═ 8.1Hz), 7.70(1H, d, J ═ 1.4Hz), 8.05(1H, d, J ═ 8.5Hz), 8.28(1H, s), preparation 62-23- (4-bromo-2-chlorophenylmethyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan

According to the same manner as in preparation example 31-3, from 3- (4-bromo-2-chlorobenzoyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (3.09g), a pale yellow oil (4.00g) containing the objective product as a main component was obtained. This material was used in the following step without purification.¹H-NMR(CDCl₃δ ppm): 2.40(3H, s), 3.89(3H, s), 4.01(2H, s), 6.89(1H, d, J ═ 8.5Hz), 7.25(1H, d, J ═ 8.3Hz), 7.42(1H, d, J ═ 8.7Hz), 7.57(1H, d, J ═ 1.9Hz), 7.94(1H, dd, J ═ 8.5 and 1.5Hz), 7.98(1H, s), preparation 62-33- (2-chloro-4-phenylbenzyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan

To unrefined 3- (4-bromo-2-chlorophenylmethyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (4.00g) was added a solution of phenylboronic acid (1.34g) in ethanol (3ml), tetrakis (triphenylphosphine)Palladium (0.40g), sodium carbonate (1.59g), water (7.50g) and toluene (30ml) were heated under reflux for 80 minutes. After cooling, the insoluble matter was removed by filtration through celite, and the filtrate was washed with ethyl acetate and water. Saturated brine was added to the filtrate, and the organic layer was separated and dried over anhydrous magnesium sulfate. Concentration gave an oil (3.50g) containing the desired product as the main component. This material was used in the following step without purification.¹H-NMR(CDCl₃δ ppm): 2.44(3H, s), 3.89(3H, s), 4.12(2H, s), 7.09-8.09(11H, m.) preparation 62-45-carboxy-3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] furan

According to the same manner as in preparation example 31-4, from unrefined 3- (2-chloro-4-phenylbenzyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (3.50g), the desired product (1.22g) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆δ ppm): 2.48(3H, s), 4.15(2H, s), 7.30(1H, d, J ═ 8.1Hz), 7.36(1H, t, J ═ 7.3Hz), 7.44(2H, t, J ═ 7.6Hz), 7.56(1H, dd, J ═ 8.0 and 1.9Hz), 7.57(1H, d, J ═ 8.6Hz), 7.66(2H, d, J ═ 7.4Hz), 7.75(1H, d, J ═ 1.9Hz), 7.82(1H, dd, J ═ 8.6 and 1.7Hz), 7.95(1H, d, J ═ 1.5Hz), preparation 633- (4-bromo-2-chlorobenzyl) -5-carboxy-2-methylbenzofuran [ b ] furan [ b ] f

The same procedures used in preparation 31-4 were repeated except for using 3- (4-bromo-2-chlorophenylmethyl) -5- (methoxycarbonyl) -2-methylbenzo [ b ] furan (1.15g) to give the desired product (0.67g) as pale yellow crystals.¹H-NMR(DMSO-d₆δ ppm): 2.44(3H, s), 4.08(2H, s), 7.18(1H, d, J ═ 8.3Hz), 7.47(1H, dd, J ═ 8.3 and 2.0Hz), 7.56(1H, d, J ═ 8.5Hz), 7.74(1H, d, J ═ 2.1Hz), 7.82(1H, dd, J ═ 8.6 and 1.7Hz), 7.89(1H, d, J ═ 1.6Hz), preparations 64-13- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2, 4-dichlorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.68g) and 2, 4-dichlorobenzyl chloride (3.29g), methyl 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.20g) and methyl 1- (2, 4-dichlorobenzyl) 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.00g) were obtained as pale yellow powders.

3- (2, 4-Dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)：2.53(3H，s)，3.99(3H，s)，5.63(2H，s)，6.60(1H，d，J＝8Hz)，7.10(1H，dd，J＝8 and 2Hz)，7.47(1H，d，J＝2Hz)，8.07(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz).

Mass(ESI)：m/e 350(M+H)⁺

1- (2, 4-Dichlorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)：2.64(3H，s)，4.02(3H，s)，5.41(2H，s)，6.43(1H，d，J＝8Hz)，7.14(1H，dd，J＝8 and 2Hz)，7.50(1H，d，J＝2Hz)，7.54(1H，d，J＝8Hz)，8.08(1H，d，J＝8Hz).

Mass(ESI)：m/e 350(M+H)⁺Preparation 64-23- (2, 4-Dichlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.17g) was used to give the desired product (1.98g) as a white powder.¹H-NMR(DMSO-d₆)：2.51(3H，s)，5.60(2H，s)，6.60(1H，d，J＝8Hz)，7.32(1H，d，J＝8Hz)，7.76(1H，s)，8.00(IH，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 334(M-H)^-Preparation example 65-12-chloro-4- (thiophen-2-yl) benzyl alcohol

By the same method as in preparation example 11-2, from 4-bromo-2-Chlorobenzenemethanol (500mg) and 2-thiopheneboronic acid (318mg) were added to give the objective product (196mg) as a pale yellow oil.¹H-NMR(CDCl₃): 1.93(1H, t, J ═ 8Hz), 4.79(2H, d, J ═ 8Hz), 7.09(1H, t, J ═ 3Hz), 7.29 to 7.34(2H, m), 7.46 to 7.54(2H, m), 7.61(1H, s), preparation 65-22-chloro-1- ((methanesulfonyloxy) methyl) -4- (thiophen-2-yl) benzene

The desired product was obtained from 2-chloro-4- (thiophen-2-yl) benzyl alcohol (196mg) according to the same method as in preparation example 14-1. The reaction mixture was used as it was in the following reaction without purification. Preparation examples 65-33- [ 2-chloro-4- (thien-2-yl) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- [ 2-chloro-4- (thien-2-yl) benzyl ] -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (148mg) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4- (thiophen-2-yl) benzene (210mg), amorphous methyl 3- [ 2-chloro-4- (thien-2-yl) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (120mg) and amorphous methyl 1- [ 2-chloro-4- (thien-2-yl) benzyl ] -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (86mg) were obtained.

3- [ 2-chloro-4- (thien-2-yl) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.58(3H，s)，4.00(2H，s)，5.69(2H，s)，6.65(1H，d，J＝8Hz)，7.08(1H，t，J＝4Hz)，7.25-7.36(3H，m)，7.69(1H，d，J＝2Hz)，8.08(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz).Mass(ESI)：m/z 398(M+1)

1- [ 2-chloro-4- (thien-2-yl) benzyl ] -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.68(3H, s), 4.01(2H, s), 5.45(2H, s), 6.50(1H, d, J ═ 8Hz), 7.09(1H, t, J ═ 4Hz), 7.28-7.39(3H, m), 7.58(1H, d, J ═ 8Hz), 7.70(1H, br), 8.08(1H, d, J ═ 8Hz). M/z 398(M +1) preparation 65-43- [ 2-chloro-4- (thien-2-yl) benzyl2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-2, methyl 3- [ 2-chloro-4- (thiophen-2-yl) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (70mg) was used to give the desired product (61mg) as colorless crystals.¹H-NMR(DMSO-d₆): 2.53(3H, s), 5.62(2H, s), 6.60(1H, d, J ═ 8Hz), 7.14(1H, t, J ═ 4Hz), 7.49(1H, d, J ═ 8Hz), 7.59(2H, d, J ═ 4Hz), 7.87(1H, d, J ═ 2Hz), 8.01(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz), mass (esi): m/z 382(M-1) mp 247-

To a suspension of methyl 3- [ 2-chloro-4- (thiophen-2-yl) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (50mg, 0.126mmol) in acetic acid (1mL) at room temperature was added N-chlorosuccinimide (19mg, 0.138 mmol). After 30 minutes, methylene chloride (0.5mL) was added to the reaction solution to form a clear solution. After 4h, N-chlorosuccinimide (19mg, 0.138mmol) was added. After standing for 1 night, the reaction solution was concentrated. The residue was purified by p-TLC (chloroform/methanol-40/1) to give the desired product as a colorless oil (52mg, 95.7%).¹H-NMR(CDCl₃): 2.56(3H, s), 3.99(2H, s), 5.69(2H, s), 6.64(1H, d, J ═ 8Hz), 6.89(1H, t, J ═ 4Hz), 7.06(1H, d, J ═ 4Hz), 7.22(1H, d, J ═ 8Hz), 7.58(1H, s), 8.08(1H, d, J ═ 8Hz), 8.16(1H, d, J ═ 8Hz), mass (esi): m/z 432(M +1) preparation 66-23- [ 2-chloro-4- (5-chlorothien-2-yl) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- [ 2-chloro-4- (5-chlorothien-2-yl) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (50mg) was purified to give the desired product (33mg) as colorless crystals.¹H-NMR(DMSO-d₆)：2.53(3H，s)，5.62(2H，s)，6.59(1H，d，J＝8Hz)，7.18(1H，d，J＝4Hz)，7.42(1H，d，J＝8Hz)，7.49(1H，d，J＝4Hz)，7.87(1H，s)，8.01(1H，d，J＝8Hz) 8.14(1H, d, J ═ 8Hz). M/z 416(M-1) mp 242-243 ℃ preparation of 67-12-chloro-4-vinylbenzyl alcohol

The same procedures used in preparation example 11-1 were repeated except for using 4-bromo-2-chlorobenzyl alcohol (2.0g) and tributyl (vinyl) tin (3.32g) to give the desired product (1.23g) as a colorless solid.¹H-NMR(CDCl₃): 1.91(1H, t, J ═ 7Hz), 4.78(2H, d, J ═ 7Hz), 5.30(1H, d, J ═ 10Hz), 5.76(1H, d, J ═ 16Hz), 6.65(1H, dd, J ═ 16,10Hz), 7.30(1H, d, J ═ 8Hz), 7.39-7.47(2H, m), preparation 67-22-chloro-1- ((methanesulfonyloxy) methyl) -4-vinylbenzene

The desired product was obtained from 2-chloro-4-vinylphenylmethanol (600mg) in the same manner as in preparation example 14-1. The reaction mixture was used in the following reaction without purification. Preparation example 67-33- (2-chloro-4-vinylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4-vinylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (478mg) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4-vinylbenzene (678mg), methyl 3- (2-chloro-4-vinylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (387mg) and amorphous methyl 1- (2-chloro-4-vinylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (264mg) were obtained as pale yellow crystals.

3- (2-chloro-4-vinylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)：2.53(3H，s)，4.00(2H，s)，5.30(1H，d，J＝10Hz)，5.67(2H，s).5.73(1H，d，J＝16Hz)，6.56-6.67(2H，m)，7.13(1H，d，J＝8Hz)，7.47(1H，d，J＝2Hz)，8.07(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz).Mass(ESI)：m/z 342(M+1)mp 185-186℃

1- (2-chloro-4-vinylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃): 2.66(3H, s), 4.01(2H, s), 5.34(1H, d, J ═ 10Hz), 5.43(2H, s), 5.76(1H, d, J ═ 16Hz), 6.47(1H, d, J ═ 10Hz), 6.61(1 h.dd, J ═ 16.10Hz), 7.15(1H, d, J ═ 8Hz), 7.50(1H, s), 7.56(1H, d, J ═ 8Hz), 8.08(1H, d, J ═ 8Hz), mass (esi): m/z 342(M +1) preparation 67-43- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

Platinum dioxide (23mg) was added to a solution of methyl 3- (2-chloro-4-vinylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (230mg, 0.67mmol) in 1, 4-dioxane (4.6ml), and catalytic reduction was carried out at room temperature. After 6 hours, filtration through celite was carried out, and the filtrate was concentrated to give black crystals. Flash silica gel column chromatography (40 ml of silica gel) was performed, and the resulting product was eluted with chloroform/ethyl acetate (5/1-4/1) and then crystallized from diisopropyl ether to give the desired product (213mg) as colorless crystals.¹H-NMR(CDCl₃): 1.20(3H, d, J ═ 8Hz), 2.53(3H, s), 2.60(2H, q, J ═ 8Hz), 3.99(3H, s), 5.65(2H, s), 6.53(1H, d, J ═ 8Hz), 6.92(1H, d, J ═ 8Hz), 7.28(1H, s), 8.05(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz), mass (esi): m/z 344(M +1) mp 172-Across 173 ℃ preparation 67-53- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, from methyl 3- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (209mg), the desired product (61mg) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆): 1.14(3H, d, J ═ 8Hz), 2.50(3H, s), 2.59(2H, q, J ═ 8Hz), 5.59(2H, s), 6.45(1H, d, J ═ 8Hz), 7.06(1H, d, J ═ 8Hz), 7.14(1H, s), 8.00(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), mass (esi): m/z 328(M-1) mp 194-196 deg.C preparation example 683- (2-chloro-4-vinylbenzyl) -2-methyl3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, from methyl 3- (2-chloro-4-vinylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (150mg), the desired product (128mg) was obtained as colorless crystals.¹H-NMR(DMSO-d₆): 2.51(3H, s), 5.32(1H, d, J ═ 10Hz), 5.60(2H, s), 5.89(1H, d, J ═ 16Hz), 6.54(1H, d, J ═ 8Hz), 6.70(1H, dd, J ═ 16,10Hz), 7.32(1H, d, J ═ 8Hz), 7.71(1H, s), 8.01(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz), mass (esi): m/z 326(M-1) mp 229-

The desired product (383mg) was obtained as a colorless oil from 2-chloro-4-methylbenzyl alcohol (259mg) in the same manner as in preparation example 14-1. ¹H-NMR(CDCl₃): preparation of 69-23- (2-chloro-4-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4-methylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (152mg) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4-methylbenzene (230mg), methyl 3- (2-chloro-4-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (74mg) and methyl 1- (2-chloro-4-methylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (80mg) were obtained as white powders.

3- (2-chloro-4-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)，2.29(3H，s)，2.51(3H，s)，3.99(3H，s)，5.64(2H，s)，6.51(1H，d，J＝8Hz)，6.90(1H，d，J＝8Hz)，7.24(1H，s)，8.05(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 330(M+H)⁺

1- (2-chloro-4-methylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)：2.32(3H，s)，2.65(3H，s)，4.01(3H，s)，5.40(2H，s)，6.41(1H，d，J＝8Hz)，6.94(1H，d，J＝8Hz)，7.28(1H，s)，7.54(1H，d，J＝8Hz)，8.06(1H，d，J＝8Hz).Mass(ESI)：m/e 330(M+H)⁺Preparation 69-33- (2-chloro-4-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (68mg) was used to give the desired product (98mg) as a white powder. ¹H-NMR(DMSO-d₆)：2.26(3H，s)，2.49(3H，s)，5.59(2H，s)，6.41(1H，d，J＝8Hz)，7.02(1H，d，J＝8Hz)，7.39(1H，s)，8.00(1H，d，J＝8Hz)，8.11(1H，d，J＝8Hz).Mass(ESI)：m/e 314(M-H)^-Preparation example 70-14-bromo-1- ((tert-butyldiphenylsiloxy) methyl) -2-chlorobenzene

Imidazole (5.34g) and tert-butylchlorodiphenylsilane (19.8g) were added to a solution of 4-bromo-2-chlorobenzyl alcohol (14.48g) in N, N-dimethylformamide (72ml) under ice-bath conditions, and stirred for 1 hour. Water was added to the reaction solution, and the product was extracted 2 times with hexane. The organic layers were combined, washed with water, saturated aqueous sodium bicarbonate solution and saturated brine in this order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, silica gel column chromatography (hexane) was performed to give the objective product (29.22g) as a colorless oil.¹H-NMR(CDCl₃): 1.10(9H, s), 4.75(2H, s), 7.32-7.50(8H, m), 7.55-7.72(5H, m.) preparation 70-21- ((tert-butyldiphenylsiloxy) methyl) -2-chloro-4- (n-pentyl) benzene

Tetrahydrofuran (5ml) was added to magnesium turnings (438mg) under a nitrogen stream, and a solution of a small amount of 4-bromo- ((tert-butyldiphenylsiloxy) methyl) -2-chlorobenzene (7.92g) in tetrahydrofuran (10ml) was added dropwise. After confirming the start of the reaction, the reaction solution was diluted with tetrahydrofuran (6.5ml), heated to 60 ℃ and the remaining raw materials were added dropwise over 45 minutes. After the completion of the dropwise addition, the reaction solution was heated under reflux for 30 minutes to obtain a tetrahydrofuran solution of 4- ((tert-butyldiphenylsiloxy) methyl) -3-chlorophenylmagnesium bromide (ca. 0.6M).

Then, 1-iodopentane (910mg) was added to a suspension of copper bromide/dimethyl sulfide complex (62mg) in hexamethylphosphoric triamide (0.3ml) under a nitrogen stream, and the mixture was heated to 60 ℃. After removing the unreacted magnesium, a solution of 4- ((tert-butyldiphenylsilyloxy) methyl) -3-chlorophenylmagnesium bromide (5ml) obtained above in tetrahydrofuran was added dropwise thereto over 10 minutes. After the completion of the dropwise addition, the reaction solution was heated under reflux for 2 hours. To the reaction solution was added an aqueous ammonium chloride solution, and the product was extracted 3 times with hexane. The organic layers were combined, washed with water and saturated brine in this order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the objective product (914mg) was obtained as a colorless oil by silica gel column chromatography (hexane).¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.11(9H, s), 1.22-1.40(4H, m), 1.52-1.68(2H, m), 2.52-2.62(2H, m), 4.80(2H, s), 7.07-7.16(2H, m), 7.31-7.48(6H, m), 7.61(1H, d, J ═ 8Hz), 7.64-7.74(4H, m), preparation 70-32-chloro-4- (n-pentyl) benzyl alcohol

To a solution of 1- ((tert-butyldiphenylsiloxy) methyl) -2-chloro-4- (n-pentyl) benzene (890mg) in tetrahydrofuran (4.5ml) was added a tetrabutylammonium fluoride/tetrahydrofuran solution (1.0M, 2.4ml) under ice-bath conditions, and the mixture was stirred for 2 hours. Water was added to the reaction solution, and the product was extracted 3 times with ethyl acetate. The organic layers were combined, washed successively with dilute hydrochloric acid, a saturated aqueous sodium bicarbonate solution and a saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 7/1) to give the desired product (345mg) as a colorless oil. ¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.21-1.41(4H，m)，1.51-1.66(2H，m)，1.90(1H，br t，J＝7Hz)，2.51-2.63(2H，m)，4.74(2H，d，J＝7Hz)，7.08(1H，d，J ═ 8Hz), 7.19(1H, s), 7.35(1H, d, J ═ 8Hz), preparation 70-42-chloro-1- ((methanesulfonyloxy) methyl) -4- (n-pentyl) benzene

The same procedure as in preparation example 14-1 was repeated, except for using 2-chloro-4- (n-pentyl) benzyl alcohol (333mg) to give the desired product (530mg) as a colorless oil.¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.22-1.44(4H, m), 1.51-1.67(2H, m), 2.52-2.64(2H, m), 2.99(3H, s), 5.31(2H, s), 7.12(1H, d, J ═ 8Hz), 7.25(1H, s), 7.38(1H, d, J ═ 8Hz), 7.38(1H, d, J ═ 8Hz) preparation 70-53- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester.

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (230mg) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4- (n-pentyl) benzene (440mg), methyl 3- (2-chloro- (n-pentyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (147mg) and methyl 1- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (176mg) were obtained as pale yellow powders.

3- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.19-1.40(4H，m)，1.48-1.64(2H，m)，2.48-2.59(2H，m)，2.53(3H，s)，3.99(3H，s)，5.65(2H，s)，6.52(1H，d，J＝8Hz)，6.90(1H，d，J＝8Hz)，7.25(1H，s)，8.07(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz).Mass(ESI)：m/e 386(M+H)⁺

1- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.19-1.40(4H，m)，1.50-1.64(2H，m)，2.49-2.61(2H，m)，2.65(3H，s)，4.01(3H，s)，5.40(2H，s)，6.42(1H，d，J＝8Hz)，6.93(1H，d，J＝8Hz)，7.29(1H，s)，7.55(1H，d，J＝8Hz)，8.07(1H，d，J＝8Hz).Mass(ESI)：m/e 386(M+H)⁺Preparation example 70-63- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (135mg) was used to give the desired product (119mg) as a white powder.¹H-NMR(DMSO-d₆)：0.84(3H，t，J＝7Hz)，1.13-1.37(4H.m)，1.43-1.60(2H，m)，2.44-2.60(2H，m)，2.50(3H，s)，5.58(2H，s)，6.45(1H，d，J＝8Hz)，7.03(1H，d，J＝8Hz)，7.39(1H，s)，8.01(1H，d，J＝8Hz)，8.12(1H，d，J＝8Hz).Mass(ESI)：m/e 370(M-H)^-Preparation 71-11- ((tert-butyldiphenylsiloxy) methyl) -2-chloro-4-isobutylbenzene

The desired product (1.644g, 76%) was obtained as a colorless oil from 4-bromo-1- ((tert-butyldiphenylsilyloxy) methyl) -2-chlorobenzene and isobutyl iodide by the same method as in preparation 70-2.¹H-NMR(CDCl₃): 0.90(6H, d, J ═ 7Hz), 1.10(9H, s), 1.75-1.96(1H, m), 2.44(2H, d, J ═ 7Hz), 4.80(2H, s), 7.03-7.11(2H, m), 7.30-7.46(6H, m), 7.56-7.74(5H, m), preparation 71-22-chloro-4-isobutylbenzyl alcohol

According to the same method as in preparation example 70-3, from 1- ((tert-butyldiphenylsilyloxy) methyl) -2-chloro-4-isobutylbenzene (1.71g), the objective product (568mg) was obtained as a colorless oil. ¹H-NMR(CDCl₃): 0.90(6H, d, J ═ 7Hz), 1.74-1.95(1H, m), 1.18(1H, br t, J ═ 7Hz), 2.44(2H, d, J ═ 7Hz), 4.75(2H, d, J ═ 7Hz), 7.05(1H, d, J ═ 8Hz), 7.16(1H, s), 7.35(1H, d, J ═ 8Hz), preparation 71-32-chloro-4-isobutyl-1- ((methanesulfonyloxy) methyl) benzene

The desired product (458mg) was obtained as a colorless oil by the same method as in preparation example 14-1 from 2-chloro-4-isobutylbenzyl alcohol (293 mg).¹H-NMR(CDCl₃)：0.90(6H，d，J＝7Hz)，1.75-1.96(1H，m)，2.48(2H，d，J＝7Hz)，3.00(3H，s)，5.31(2H，s)，7.09(1H，d，J＝8Hz)，7.22(1H, s), 7.39(1H, d, J ═ 8Hz) preparation 71-43- (2-chloro-4-isobutylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4-isobutylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (212mg) and 2-chloro-4-isobutyl-1- ((methanesulfonyloxy) methyl) benzene (390mg), 3- (2-chloro-4-isobutylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (124mg) and 1- (2-chloro-4-isobutylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (152mg) were obtained as pale yellow powders.

3- (2-chloro-4-isobutylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester ¹H-NMR(CDCl₃)：0.88(6H，d，J＝7Hz)，1.71-1.90(1H，m)，2.40(2H，d，J＝7Hz)，2.52(3H，s)，3.99(3H，s)，5.64(2H，s)，6.53(1H，d，J＝8Hz)，6.87(1H，d，J＝8Hz)，7.21(1H，s)，8.05(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 372(M+H)⁺

1- (2-chloro-4-isobutylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine 5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：0.88(6H，d，J＝7Hz)，1.71-1.92(1H，m)，2.42(2H，d，J＝7Hz)，2.65(3H，s)，4.00(3H，s)，5.41(2H，s)，6.41(1H，d，J＝8Hz)，6.90(1H，d，J＝8Hz)，7.24(1H，s)，7.55(1H，d，J＝8Hz)，8.07(1H，d，J＝8Hz).Mass(ESI)：m/e 372(M+H)⁺Preparation 71-53- (2-chloro-4-isobutylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, from methyl 3- (2-chloro-4-isobutylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (116mg), the desired product (122mg) was obtained as a white powder.¹H-NMR(DMSO-d₆)：0.82(6H，d，J＝7Hz)，1.68-1.89(1H.m)，2.42(2H，d，J＝7Hz)，2.50(3H，s)，5.59(2H，s)，6.44(1H，d，J＝8Hz)，7.01(1H，d，J＝8Hz)，7.36(1H，s)，8.00(1H，d，J＝8Hz)，8.12(1H，d，J＝8H).Mass(ESI)：m/e 356(M-H)^-Preparation example 72-11- ((tert-butyldiphenylsiloxy) methyl) -2-chloro-4- (cyclohexylmethyl) benzene

The desired product (797mg, 56%) was obtained as a colorless oil from 4-bromo-1- ((tert-butyldiphenylsilyloxy) methyl) -2-chlorobenzene and cyclohexylmethylsulphone in the same manner as in preparation 70-2.¹H-NMR(CDCl₃): 0.82 to 1.75(11H, m), 1.11(9H, s), 2.45(2H, d, J ═ 7Hz), 4.79(2H, s), 7.03 to 7.11(2H, m), 7.31 to 7.48(6H, m), 7.61(1H, d, J ═ 8Hz), 7.63 to 7.73(4H, m), preparation 72-22-chloro-4- (cyclohexylmethyl) benzyl alcohol

From 1- ((tert-butyldiphenylsiloxy) methyl) -2-chloro-4- (cyclohexylmethyl) benzene (1.03g), the objective product (378mg) was obtained as a colorless oil by the same method as in preparation example 70-3.¹H-NMR(CDCl₃): 0.82 to 1.74(11H, m), 1.87(1H, br t, J ═ 7Hz), 2.44(2H, d, J ═ 7H2), 4.74(2H, d, J ═ 7Hz), 7.04(1H, d, J ═ 8Hz), 7.15(1H, s), 7.34(1H, d, J ═ 8Hz), preparation 72-32-chloro-4- (cyclohexylmethyl) -1- ((methanesulfonyloxy) methyl) benzene

The same procedure as in preparation example 14-1 was repeated except for using 2-chloro-4- (cyclohexylmethyl) benzyl alcohol (365mg) to give the desired product (543mg) as a colorless oil.¹H-NMR(CDCl₃): 0.80-1.75(11H, m), 2.46(2H, d, J ═ 7Hz), 2.99(3H, s), 5.30(2H, s), 7.08(1H, d, J ═ 8Hz), 7.20(1H, s), 7.38(1H, d, J ═ 8Hz), preparation 72-43- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (170mg) and 1- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (229mg) and 2-chloro-4- (cyclohexylmethyl) -1- ((methanesulfonyloxy) methyl) benzene (469mg), methyl 3- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (170mg) and methyl 1- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (222mg) were obtained as pale yellow powders.

3- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：0.80-1.74(11H，m)，2.40(2H，d，J＝7Hz)，2.53(3H，s)，3.99(3H，s)，5.64(2H，s)，6.52(1H，d，J＝8Hz)，6.86(1H，d，J＝8Hz)，7.21(1H，s)，8.05(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 412 (M+H)⁺

1- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester ¹H-NMR(CDCl₃)：0.80-1.75(11H，m)，2.43(2H，d，J＝7Hz)，2.65(3H，s)，4.01(3H，s)，5.04(2H，s)，6.40(1H，d，J＝8Hz)，6.89(1H，d，J＝8Hz)，7.24(1H，s)，7.56(1H，d，J＝8Hz)，8.07(1H，d，J＝8Hz).Mass(ESI)：m/e 412 (M+H)⁺Preparation example 72-53- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (156mg) was used to give the desired product (180mg) as a white powder.¹H-NMR(DMSO-d₆)：0.78-1.68(11H，m)，2.42(2H，d，J＝7Hz)，2.50(3H，s)，5.58(2H，s)，6.44(1H，d，J＝8Hz)，7.00(1H，d，J＝8Hz)，7.35(1H，s)，8.01(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 396(M-H)^-Preparation example 73-14-bromo-1- ((tert-butyldimethylsiloxy) methyl) -2-chlorobenzene

The same procedures used in preparation 70-1 were repeated except for using 4-bromo-2-chlorobenzyl alcohol (4.42g) to give the desired product (6.10g) as a colorless oil.¹H-NMR(CDCl₃): 0.12(6H, s), 0.95(9H, s), 4.71(2H, s), 7.37-7.50(3H, m.) preparation 73-24- ((tert-butyldimethylsilyloxy) methyl) -3-chlorobenzaldehyde

To a solution of 4-bromo-1- ((tert-butyldimethylsiloxy) methyl) -2-chlorobenzene (4.03g) in tetrahydrofuran (10ml) was added an n-butyllithium/hexane solution (1.6M, 8.3ml) under a nitrogen stream at-60 ℃ and stirred for 45 minutes. Once the reaction solution was raised to 0 ℃ and cooled again to-40 ℃, 1-formylpiperidine (1.63g) was added dropwise over 3 minutes. After that, the reaction solution was raised to 0 ℃ over 2 hours. An aqueous ammonium chloride solution was added to the reaction solution, and the product was extracted 2 times with hexane. The organic layers were combined, washed successively with dilute hydrochloric acid, a saturated aqueous sodium bicarbonate solution and a saturated brine, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the objective product (2.49g) was obtained as a colorless oil by silica gel column chromatography (hexane/ethyl acetate: 30/1). ¹H-NMR(CDCl₃)：0.16(6H，s)，0.98(9H，s)，4.83(2H，s)，7.70-7.86(3H，m)，9.96(1H，s).Mass(ESI)：m/e 283(M-H)^-Preparation 73-3(E) -1- ((tert-butyldimethylsilyloxy) methyl) -2-chloro-4- (2-phenylvinyl) benzene

Sodium hydride (70% in mineral oil, 81mg) was added to a mixed solution of 4- ((tert-butyldimethylsilyloxy) methyl) -3-chlorobenzaldehyde (571mg) and diethyl benzylphosphate (502mg) in N, N-dimethylformamide (2ml) under a nitrogen stream at room temperature, and stirred at 40 ℃ for 2 hours. Water was added to the reaction solution, and the product was extracted with ether 3 times. The organic layers were combined, washed with water and saturated brine in this order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the objective product (448mg) was obtained as a colorless oil by silica gel column chromatography (hexane/ethyl acetate 50/1).¹H-NMR(CDCl₃): 0.14(6H, s), 0.97(9H, s), 4.80(2H, s), 7.03(1H, d, J ═ 16Hz), 7.10(1H, d, J ═ 16Hz), 7.26 to 7.58(8H, m), preparation 73-4(E) -2-chloro-4- (2-phenylvinyl) benzyl alcohol

From (E) -1- ((tert-butyldimethylsilyloxy) methyl) -2-chloro-4- (2-phenylvinyl) benzene (745mg) according to the same method as in preparation example 70-3, the objective product (422mg) was obtained as a white powder.¹H-NMR(CDCl₃)：1.91(1H，br t，J＝7Hz)，4.79(2H，d，J＝7Hz)，7.02(1H，d，J＝16Hz)，7.12(1H, d, J ═ 16Hz), 7.24-7.55(8H, m), preparation 73-5(E) -2-chloro-1- ((methanesulfonyloxy) methyl) -4- (2-phenylethenyl) benzene

From (E) -2-chloro-4- (2-phenylvinyl) benzyl alcohol (412mg), the desired product (583mg) was obtained as a white solid in the same manner as in preparation example 14-1.¹H-NMR(CDCl₃): 3.01(3H, s), 5.34(2H, s), 7.02(1H, d, J ═ 16Hz), 7.14(1H, d, J ═ 16Hz), 7.27-7.61(8H, m), preparation 73-6(E) -3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and (E) -1- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (250mg) and (E) -2-chloro-1- ((methanesulfonyloxy) methyl) -4- (2-phenylvinyl) benzene (518mg), methyl (E) -3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (163mg) and (E) -1- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-1H-imidazo [ 4 ] were obtained as white powders, 5-b ] pyridine-5-carboxylic acid methyl ester (194 mg).

(E) -methyl 3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate:¹H-NMR(CDCl₃)：2.54(3H，s)，3.99(3H，s)，5.68(2H，s)，6.61(1H，d，J＝8Hz)，6.97(1H，d，J＝16Hz)，7.08(1H，d，J＝16Hz)，7.16-7.62(7H，m)，8.08(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz).Mass(ESI)：m/e 418(M+H)⁺

(E) -methyl 1- (2-chloro-4- (phenylvinyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate: ¹H-NMR(CDCl₃)：2.65(3H，s)，4.01(3H，s)，5.44(2H，s)，6.48(1H，d，J＝8Hz)，6.97(1H，d，J＝16Hz)，7.10(1H，d，J＝16Hz)，7.19-7.64(8H，m)，8.08(1H，d，J＝8Hz).Mass(ESI)：m/e 418(M+H)⁺Preparation example 73-7(E) -3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyri-dinePyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, from (E) -methyl 3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (158mg), the desired product (149mg) was obtained as a white powder.¹H-NMR(DMSO-d₆)：2.52(3H，s)，5.63(2H，s)，6.59(1H，d，J＝8Hz)，7.16-7.48(6H，m)，7.53-7.63(2H，m)，7.84(1H，s)，8.01(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz).Mass(ESI)：m/e 402(M-H)^-Preparation example 74-12-chloro-4-hydroxybenzoic acid

4-amino-2-chlorobenzoic acid (10.01g) was dissolved in 12.5% sulfuric acid (400ml) by heating to 70 ℃ and then cooled with ice. An aqueous solution of sodium nitrite (4.24 g/water 12ml) was added dropwise to the suspension at 8 ℃ or lower over 5 minutes. After 5 minutes, the solution was slowly poured into 80 ℃ water (500ml) and vigorously bubbled to become a red solution. The reaction solution was stirred at 80 ℃ for 1 hour. After cooling, the product was extracted 3 times with ether. The organic layers were combined, washed with dilute hydrochloric acid, water and saturated brine in this order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, a small amount of diisopropyl ether was added thereto and the mixture was crystallized to obtain the desired product (6.32g) as an orange powder.¹H-NMR(DMSO-d₆)：6.79(1H，dd，J＝8 and 2Hz)，6.88(1H，d，J＝2Hz)，7.77(1H，d，J＝8Hz).Mass(ESI)：m/e 171(M-H)^-Preparation example 74-24-Phenylmethoxy-2-Chlorobenzoic acid phenylmethyl ester

To a solution of 2-chloro-4-hydroxybenzoic acid (695mg) in N, N-dimethylformamide (3.5ml) were added potassium carbonate (1.67g) and benzyl bromide (1.73g), and the mixture was stirred at room temperature for 14 hours. 1N hydrochloric acid was added to the reaction solution, and the product was extracted with ether 3 times. The organic layers were combined, washed with water, saturated aqueous sodium bicarbonate solution and saturated brine in this order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was recrystallized from diisopropyl ether/hexane to give the desired product (1.13g) as a pale yellow powder. ¹H-NMR(CDCl₃)：5.09(2H，s)，5.32(2H，s)，6.87(1H，dd，J＝8 and 2Hz)，7.05(1H，d，J＝2Hz)，7.29-7.50(10H，m)，7.91(1H，d，J＝8Hz).Mass(ESI)：m/e 353(M+H)⁺Preparation example 74-34-Phenylmethoxy-2-Chlorobenzoic acid

To 4-benzyloxy-2-chlorobenzoic acid benzyl ester (1.12g) were added ethanol (8.8ml), 1, 4-dioxane (2.2ml) and a 1N aqueous solution of sodium hydroxide (4.7ml), and the mixture was stirred at 70 ℃ for 1.5 hours. After the solvent was distilled off, the residue was dissolved in water and washed with diethyl ether. The aqueous layer was made acidic with 1N hydrochloric acid, and the precipitated precipitate was collected by filtration to give the objective product (810mg) as a pale yellow powder.¹H-NMR(DMSO-d₆)：5.20(2H，s)，7.06(1H，dd，J＝8 and 2Hz)，7.18(1H，d，J＝2Hz)，7.29-7.50(5H，m)，7.82(1H，d，J＝8Hz).Mass(ESI)：m/e 261(M-H)^-Preparation example 74-44-Phenylmethoxy-2-chlorobenzyl alcohol

Borane/dimethyl sulfide complex (10.0M, 0.6ml) was added dropwise to a tetrahydrofuran (7.9ml) solution of 4-benzyloxy-2-chlorobenzoic acid (788mg) under a nitrogen atmosphere at room temperature, and the mixture was refluxed for 2.5 hours. After the reaction solution was allowed to cool to room temperature, 1N hydrochloric acid (1.5ml) was added dropwise with great care, and the mixture was stirred for 30 minutes. Water was added to the reaction solution, and the product was extracted with ethyl acetate 3 times and dried over anhydrous magnesium sulfate. The solvent was distilled off to leave the desired product (778mg) as a white powder.¹H-NMR(CDCl₃): 1.83(1H, br t, J ═ 7Hz), 4.70(2H, d, J ═ 7Hz), 5.05(2H, s), 6.88(1H, dd, J ═ 8 and 2Hz), 7.01(1H, d, J ═ 2Hz), 7.28-7.46(6H, m), preparation 74-54-benzyloxy-2-chlorophenylmethyl chloride

The desired product (639mg) was obtained as a colorless oil from 4-benzyloxy-2-chlorobenzyl alcohol (523mg) according to the same method as in preparation example 14-1.¹H-NMR(CDCl₃): 4.67(2H, s), 5.05(2H, s), 6, 87(1H, dd, J. cndot.8 and 2Hz), 7.02(1H, d, J. cndot.2 Hz), 7.28-7.44(6H, m.) preparation 74-63- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (229mg) and 4-benzyloxy-2-chlorobenzyl chloride (509mg), methyl 3- (4-benzyloxy-2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (130mg) and methyl 1- (4-benzyloxy-2-chlorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (141mg) were obtained as pale yellow powders.

3- (4-Phenylmethoxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.53(3H，s)，4.00(3H，s)，5.01(2H，s)，5，62(2H，s)，6.63(1H，d，J＝8Hz)，6.72(1H，dd，J＝8 and 2Hz)，7.06(1H，d，J＝2Hz)，7.30-7.42(5H，m)，8.04(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 422(M+H)⁺

1- (4-Phenylmethoxy-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.66(3H，s)，4.01(3H，s)，5.02(2H，s)，5.38(2H，s)，6.48(1H，d，J＝8Hz)，6.75(1H，dd，J＝8 and 2Hz)，7.08(1H，d，J＝2Hz)，7.28-7.47(5H，m)，7.54(1H，d，J＝8Hz)，8.06(1H，d，J＝8Hz).Mass(ESI)：m/e 422(M+H)⁺Preparation example 74-73- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (116mg) was used to obtain the desired product (110mg) as a white powder.¹H-NMR(DMS0-d₆)：2.39(3H，s)，5.08(2H，s)，5.51(2H，s)，6.41(1H，d，J＝8Hz)，6.88(1H，dd，J＝8 and 2Hz)，7.23(1H，d，J＝2Hz)，7.28-7.45(5H，m)，7.85(2H，s).Mass(ESI)：m/e 406(M-H)^-Preparation example 75-13- (2-chloro-4-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4-methoxybenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (145mg) and 2-chloro-4-methoxybenzyl bromide (215mg), methyl 3- (2-chloro-4-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (62mg) and methyl 1- (2-chloro-4-methoxybenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (62mg) were obtained as white powders.

3- (2-chloro-4-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDC1₃)：2.52(3H，s)，3.77(3H，s)，4.00(3H，s)，5.61(2H，s)，6.65(2H，s)，6.97(1H，s)，8.04(1H，d，J＝8Hz)，8.12(1H，d，J＝8Hz).Mass(ESI)：m/e 346(M+H)⁺

1- (2-chloro-4-methoxybenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.65(3H，s)，3.78(3H，s)，4.01(3H，s)，5.38(2H，s)，6.51(1H，d，J＝8Hz)，6.68(1H，dd，J＝8 and 2Hz)，7.00(1H，d，J＝2Hz)，7.54(1H，d，J＝8Hz)，8.04(1H，d，J＝8Hz).Mass(ESI)：m/e 346(M+H)⁺Preparation example 75-23- (2-chloro-4-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (78mg) was used to give the desired product (83mg) as a white powder. ¹H-NMR(DMSO-d₆)：2.50(3H，s)，3.55(3H，s)，5.53(2H，s)，6.58(1H，d，J＝8Hz)，6.81(1H，dd，J＝8 and 2Hz)，7.13(1H，d，J＝2Hz)，7.99(1H，d，J＝8Hz).8.11(1H，d，J＝8Hz).Mass(ESI)：m/e 330(M-H)^-Preparation example 76-12-chloro-4-isopropoxybenzoin isopropyl ester

The same procedures used in preparation example 74-2 were repeated except for using 2-chloro-4-hydroxybenzoic acid (500mg) and isopropyl iodide (1.18g) to give the desired product (839mg) as a pale brown oil.¹H-NMR(CDCl₃)：1.36(12H，m)，4.59(1H，m)，4.59(1H，m)，5.24(1H，m)，6.78(1H，d，J＝8Hz)，6.93(1H, s), 7.82(1H, d, J ═ 8 Hz.) preparation 76-22-chloro-4-isopropoxybenzyl alcohol

Lithium aluminum hydride (100mg) was added to a solution of isopropyl 2-chloro-4-isopropoxybenzoin (675mg) in diethyl ether (6.8ml) under ice-bath conditions, and stirred under the same conditions for 2 hours. To the reaction mixture were added water (0.8ml), a 1N aqueous solution of sodium hydroxide (0.8ml), and water (2.4ml) in this order under ice-bath conditions, followed by stirring at room temperature for 30 minutes, followed by addition of ether and water, and separation of an organic layer. The product was extracted from the aqueous layer with ether, and the organic layers were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off to leave the desired product (513mg) as a brown oil.¹H-NMR(CDCl₃): 1.32(6H, d, J ═ 6Hz), 1.97(1H, t, J ═ 6Hz), 4.52(1H, m), 4.70(2H, d, J ═ 6Hz), 6.78(1H, dd, J ═ 2Hz), 6.92(1H, d, J ═ 2Hz), 7.33(1H, d, J ═ 8Hz), preparation 76-32-chloro-4-isopropoxybenzyl chloride

Pyridine (0.5ml) and thionyl chloride (0.18mg) were added in this order to a dichloromethane (2ml) solution of 2-chloro-4-isopropoxybenzyl alcohol (401mg) under ice-bath conditions, and stirred under the same conditions for 1 hour. Water was added to the reaction solution, and the product was extracted 3 times with hexane. The organic layers were combined, washed successively with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and a saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off to leave the objective product (353mg) as a yellow oil. ¹H-NMR(CDCl₃): 1.32(6H, d, J ═ 7Hz), 4.52(1H, sept, J ═ 7Hz), 4.65(2H, s), 6.76(1H, dd, J ═ 8 and 2Hz), 6.91(1H, d, J ═ 2Hz), 7.32(1H, d, J ═ 8.5Hz), preparation of methyl 76-43- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate and methyl 1- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] 5-carboxylate

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (194mg) and 2-chloro-4-isopropoxybenzyl chloride (340mg), methyl 3- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (73mg) and methyl 1- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (80mg) were obtained as white powders.

3- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：1.29(6H，d，J＝7Hz)，2.54(3H，s)，4.00(3H，s)，4.47(1H，sept，J＝7Hz)，5.61(2H，s)，6.62(2H，s)，6.95(1H，s)，8.05(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 374(M+H)⁺

1- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] -5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：1.30(6H，d，J＝7Hz)，2.65(3H，s)，4.00(3H，s)，4.48(1H，sept，J＝7Hz)，5.35(2H，s)，6.47(1H，d，J＝8Hz)，6.64(1H，dd，J＝8 and 2Hz)，6.98(1H，d，J＝2Hz)，7.54(1H，d，J＝8Hz)，8.06(1H，d，J＝8Hz).Mass(ESI)：m/e 374(M+H)⁺Preparation example 76-53- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, from methyl 3- (2-chloro-4-isopropoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (67mg), the desired product (66mg) was obtained as a pale yellow powder. ¹H-NMR(DMSO-d₆)：1.23(6H，d，J＝7Hz)，2.50(3H，s)，4.60(1H，sept，J＝7Hz)，5.53(2H，s)，6.52(1H，d，J＝8Hz)，6.79(1H，dd，J＝8 and 2Hz)，7.11(1H，d，J＝2Hz)，8.01(1H，d，J＝8Hz)，8.12(1H，d，J＝8Hz).Mass(ESI)：m/e 358(M-H)^-Preparation example 77-14- (n-butoxy) -2-chlorobenzoic acid n-butyl ester

The same procedures used in preparation example 74-2 were repeated except for using 2-chloro-4-hydroxybenzoic acid (500mg) and n-butylsulfanyl (1.28g) to give the desired product (839mg) as a pale brown oil.¹H-NMR(CDCl₃): 0.98(6H, t, J ═ 6Hz), 1.48(4H, m), 1.76(4H, m), 3.99(2H, t, J ═ 6Hz), 4.30(2H, t, J ═ 6Hz), 6.80(1H, d, J ═ 8Hz), 6.95(1H, s), 7.86(1H, d, J ═ 8Hz)77-24-n-butoxy-2-chlorobenzol

The same procedure as in preparation 80-2 was repeated, except for using n-butyl 4- (n-butyl) -2-chlorobenzoate (835mg) to give the objective product (513mg) as a brown oil.¹H-NMR(CDCl₃): 0.98(3H, t, J ═ 6Hz), 1.48(2H, m), 1.76(2H, m), 1.86(1H, t, J ═ 6Hz), 3.95(2H, t, J ═ 6Hz), 4.71(2H, d, J ═ 6Hz), 6.80(1H, d, J ═ 8Hz), 6.93(1H, s), 7.34(1H, d, J ═ 8Hz), preparation 77-34-n-butoxy-2-chlorobenzyl chloride

The same procedures used in preparation example 14-1 were repeated except for using 4- (n-butoxy) -2-chlorobenzyl alcohol (475mg) to give the desired product (505mg) as a colorless oil.¹H-NMR(CDCl₃): 0.98(3H, t, J ═ 7Hz), 1.38 to 1.56(2H, m), 1.68 to 1.82(2H, m), 3.95(2H, t, J ═ 7Hz), 4.67(2H, s), 6.78(1H, dd, J ═ 8 and 2Hz), 6.92(1H, d, J ═ 2Hz), 7.33(1H, d, J ═ 8Hz), preparation examples 77-43- (4- (n-butoxy) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (4- (n-butoxy) -2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (230mg) and 4- (n-butoxy) -2-chlorobenzyl chloride (443mg), methyl 3- (4- (n-butoxy) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (105mg) and methyl 1- (4- (n-butoxy) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (111mg) were obtained as pale yellow powders.

3- (4- (n-butoxy) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：0.96(3H，t，J＝7Hz)，1.38-1.54(2H，m)，1.65-1.81(2H，m)，2.52(3H，s)，3.90(2H，t，J＝7Hz)，4.00(3H，s)，5.60(2H，s)，6.63(2H，s)，6.95(1H，s)，8.04(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 388(M+H)⁺

1- (4- (n-butoxy) -2-chlorophenylmethyl)) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：0.95(3H，t，J＝7Hz)，1.38-1.53(2H，m).1.66-1.81(2H，m)，2.65(3H，s)，3.92(2H，t，J＝7Hz)，4.01(3H，s)，5.37(2H，s)，6.48(1H，d，J＝8Hz).6.67(1H，dd，J＝8 and 2Hz)，6.99(1H，d，J＝2Hz)，7.55(1H，d，J＝8Hz)，8.06(1H，d，J＝8Hz).Mass(ESI)：m/e 388(M+H)⁺Preparation example 77-53- (4-n-butoxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4- (n-butoxy) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (90mg) was used to give the desired product (90mg) as a pale yellow powder.¹H-NMR(DMSO-d₆)：0.90(3H，t，J＝7Hz)，1.30-1.48(2H，m)，1.57-1.71(2H，m)，2.50(3H，s)，3.94(2H，t，J＝7Hz)，5.54(2H，s)，6.53(1H，d，J＝8Hz)，6.80(1H，dd，J＝8 and 2Hz)，7.13(1H，d，J＝2Hz)，8.00(1H，d，J＝8Hz)，8.11(1H，d，J＝8Hz).Mass(ESI)：m/e 372(M-H)^-Preparation example 78-12-chloro-4- ((cyclohexylmethyl) oxy) benzoic acid cyclohexylmethyl ester

The same procedures used in preparation 74-2 were repeated except for using 2-chloro-4-hydroxybenzoic acid (500mg) and isopropyl bromide (1.23g) to give the desired product (1.14g) as a pale brown oil. ¹H-NMR(CDCl₃): 1.08(4H, m), 1.26(6H, m), 1.78(12H, m), 3.78(2H, d, J ═ 6Hz), 4.12(2H, d, J ═ 6Hz), 6.80(1H, d, J ═ 8Hz), 6.96(1H, s), 7, 88(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 80-2 described below, from cyclohexylmethyl 2-chloro-4- ((cyclohexylmethyl) oxybenzoate (1.13g), the objective product (903mg) was obtained as a brown oil.¹H-NMR(CDCl₃): 0.85-1.90(11H, m), 3.44(1H, t, J ═ 6Hz), 3.73(2H, d, J ═ 6Hz), 4.70(2H, d, J ═ 6Hz), 6.79(1H, dd, J ═ 8,1Hz), 6.92(1H, d, J ═ 1Hz), 7.33(1H, d, J ═ 8Hz), preparation 78-32-chloro-4- ((cyclohexyl) methoxy) phenylmethyl chloride

The desired product (844mg) was obtained as a colorless oil from 2-chloro-4- ((cyclohexylmethyl) oxy) benzyl alcohol (855mg) in the same manner as in preparation example 76-3.¹H-NMR(CDCl₃): 0.82-1.91(11H, m), 3.72(2H, d, J ═ 7Hz), 4.66(2H, s), 6.78(1H, dd, J ═ 8 and 2Hz), 6.92(1H, d, J ═ 2Hz), 7.32(1H, d, J ═ 8Hz), preparation 78-43- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] 5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (194mg) and 2-chloro-4- ((cyclohexylmethyl) oxy) phenylmethyl chloride (403mg), methyl 3- (2-chloro-4- ((cyclohexylmethyl) oxy) phenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (58mg) and methyl 1- (2-chloro-4- ((cyclohexylmethyl) oxy) phenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] -5-carboxylate (36mg) were obtained as colorless oils.

3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：0.90-1.90(11H，m)，2.52(3H，s)，3.69(2H，d，J＝7Hz)，3.99(3H，s)，5.61(2H，s)，6.62(2H，s)，6.95(1H，s)，8.04(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 428(M+H)⁺

1- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：0.92-1.92(11H，m)，2.64(3H，s)，3.69(2H，d，J＝7Hz)，4.00(3H，s)，5.37(2H，s)，6.48(1H，d，J＝8Hz)，6.65(1H，dd，J＝8 and 2Hz)，6.98(1H，d，J＝2Hz)，7.53(1H，d，J＝8Hz)，8.04(1H，d，J＝8Hz).Mass(ESI)：m/e 428(M+H)⁺Preparation example 78-53- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to preparation example 4-In the same manner as in 7, methyl 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (53mg) was used to give the desired product (53mg) as a pale yellow powder.¹H-NMR(DMSO-d₆)：0.90-1.82(11H，m)，2.50(3H，s)，3.76(1H，d，J＝7Hz).5.53(2H，s)，6.54(1H，d，J＝8Hz)，6.80(1H，dd，J＝8 and 2Hz)，7.12(1H，d，J＝2Hz)，8.00(1H，d，J＝8Hz)，8.11(1H，d，J＝8Hz).Mass(ESI)：m/e 412(M-H)^-Preparation example 79-12-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzaldehyde

To a solution of 2- [ N- (2-hydroxyethyl) -N-methylamino ] pyridine (3.87g) in dry N, N-dimethylformamide (39ml) was added sodium hydride (60% in oil, 1.12g), and the mixture was stirred at room temperature for 30 minutes. 2-chloro-4-fluorobenzaldehyde (4.43g) was added to the reaction mixture, and after stirring for 3 days, it was diluted with ethyl acetate and washed with water. The aqueous layer was extracted 2 times with ethyl acetate, and the organic layers were combined, dried over magnesium sulfate, and concentrated and dried under reduced pressure to solidify. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 9/1) to give the desired product (3.30g) as a pale yellow oil. ¹H-NMR(CDCl₃): 3.13(3H, s), 4.01(2H, t, J ═ 6Hz), 4.28(2H, t, J ═ 6Hz), 6.52(1H, d, J ═ 8Hz), 6.60(1H, dd, J ═ 8, 5Hz), 6.90(1H, dd, J ═ 8, 2Hz), 7.02(1H, d, J ═ 8, 2Hz), 7.48(1H, t, J ═ 8Hz), 7.87(1H, d, J ═ 8Hz), 8.18(1H, d, J ═ 5Hz), 10.00(1H, s). preparative example 79-22-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl alcohol

To a solution of 2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzaldehyde (438mg) in ethanol (3ml) was added sodium borohydride (58mg) at room temperature, and the mixture was stirred for 2 hours. 1N hydrochloric acid (1.5ml) was added dropwise to the reaction mixture to decompose the excess reagent, and then the whole was diluted with ethyl acetate. Saturated aqueous sodium bicarbonate was added to neutralize and the product was extracted 2 times with ethyl acetate. The organic layers were combined, washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off to leave the desired product (437mg) as a colorless oil.¹H-NMR(CDCl₃)：3.12(3H，s)，3.97(2H，t，J＝5Hz)，4.17(2H，t，J＝5Hz)，4.70(2H，s)，6.51(1H，d，J＝8Hz)，6.58(1H，dd，J＝8 and 5Hz)，6.79(1H，dd，J＝8 and 2Hz)，6.97(1H，d，J＝2Hz)，7.32(1H，d，J＝8Hz)，7.46(1H，t，J＝8Hz)，8.16(1H，d，J＝5Hz).Mass(ESI)：m/e 293(M+H)⁺Preparation example 79-32-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) phenylmethyl chloride

The same procedure used in preparation example 76-3 was repeated except for using 2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl alcohol (557mg), to give the desired product (662mg) as a pale yellow oil. ¹H-NMR(CDCl₃): 3.13(3H, s).3.99(2H, t, J ═ 5Hz), 4.19(2H, t, J ═ 5Hz), 4.65(2H, s), 6.51(1H, d, J ═ 8Hz), 6.58(1H, dd, J ═ 8 and 5Hz), 6.79(1H, dd, J ═ 8 and 2Hz), 7.00(1H, d, J ═ 2Hz), 7.31(1H, d, J ═ 8Hz), 7.47(1H, t, J ═ 8Hz), 8.17(1H, d, J ═ 5Hz), preparation 79-43- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine carboxylic acid methyl ester and N- (2-chloro-4- ((2-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-pyridine ] carboxylic acid methyl ester -pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (290mg) and 2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) phenylmethyl chloride (577mg), methyl 3- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) phenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (156mg) and 1- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) phenylmethyl) pyridine-5-carboxylate (156mg) were obtained as colorless oils -methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (160 mg).

3- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)：2.51(3H，s)，3.11(3H，s)，3.95(2H，t，J＝5Hz)，3.99(3H，s)，4.14(2H，t，J＝5Hz)，5.60(2H，s)，6.49(1H，d，J＝8Hz)，6.55(1H，dd，J＝8 and 5Hz)，6.63(2H，s)，7.02(1H，s)，7.44(1H，t，J＝8Hz)，8.04(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz)，8.15(1H，d，J＝5Hz).Mass(ESI)：m/e 466(M+H)⁺

1- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)：2.64(3H，s)，3.11(3H，s)，3.95(2H，t，J＝5Hz)，4.01(3H，s)，4.15(2H，t，J＝5Hz)，5.35(2H，s)，6.45-6.60(3H，m)，6.68(1H，dd，J＝8 and 2Hz)，7.08(1H，d，J＝2Hz)，7.44(1H，t，J＝8Hz)，7.52(1H，d，J＝8Hz)，8.01(1H，d，J＝2Hz)，8.04(1H，d，J＝8Hz).Mass(ESI)：m/e 466(M+H)⁺Preparation example 79-53- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (143mg) was used to obtain the desired product (114mg) as a white powder.¹H-NMR(DMSO-d₆)：2.50(3H，s)，3.03(3H，s)3.87(2H，t，J＝5Hz)，4.13(2H，t，J＝5Hz)，5.53(2H，s)，6.50-6.65(3H，m)，6.82(1H，dd，J＝8 and 2Hz)，7.20(1H，d，J＝2Hz)，7.49(1H，t，J＝8Hz)，7.99(1H，d，J＝8Hz)，8.06(1H，d，J＝5Hz)，8.10(1H，d，J＝8Hz).Mass(ESI)：m/e 450(M-H)^-Preparation example 80-12-chloro-4- (methylthio) benzoic acid methyl ester

Sodium thiomethoxide (459mg) was added to a solution of methyl 4-bromo-2-chlorobenzoate (1.25g) in N, N-dimethylformamide (10ml) under ice-bath conditions, and stirred under the same conditions for 2 hours. 1N hydrochloric acid was added to the reaction solution, and the product was extracted with ether 3 times. Combination of Chinese herbsThe organic layer was washed with water and saturated brine in this order, and dried over anhydrous magnesium sulfate. The solvent was distilled off, and then the residue was purified by silica gel column chromatography (hexane/ethyl acetate: 10/1) to give the desired product (835mg) as a colorless oil.¹H-NMR(CDCl₃): 2.49(3H, s), 3.90(3H, s), 7.11(1H, d, J ═ 8Hz), 7.23(1H, s), 7.78(1H, d, J ═ 8Hz)

Methyl 2-chloro-4- (methylthio) benzoate (806mg) was added dropwise to a tetrahydrofuran (8ml) suspension of lithium aluminum hydride (139mg) under ice-water bath conditions, and stirred under the same conditions for 1 hour. After diluting the reaction solution with diethyl ether, 1N hydrochloric acid (10ml) was added dropwise, and the product was extracted with diethyl ether 3 times. The organic layers were combined, washed successively with a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off to leave the objective product (725mg) as a colorless oil.¹H-NMR(CDCl₃): 1.92(1H, br t, J ═ 7Hz), 2.48(3H, s), 4.73(2H, d, J ═ 7Hz), 7.15(1H, d, J ═ 8Hz), 7.23(1H, s), 7.37(1H, d, J ═ 8Hz), preparation 80-32-chloro-1- ((methanesulfonyloxy) methyl) -4- (methylthio) benzene

The same procedures used in preparation example 14-1 were repeated except for using 2-chloro-4- (methylthio) benzyl alcohol (687mg) to give the desired product (1.02g) as a colorless oil.¹H-NMR(CDCl₃): examples of preparation 80-43- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4- (methylthio) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (3H, s), 3.00(3H, s), 5.30(2H, s), 7.15(1H, dd, J ═ 8 and 2Hz), 7.26(1H, d, J ═ 2Hz), 7.38(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (573mg) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4- (methylthio) benzene (955mg), methyl 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (457mg) and methyl 1- (2-chloro-4- (methylthio) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (402mg) were obtained as white powders.

3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.44(3H，s)，2.53(3H，s).4.00(3H，s)，5.63(2H，s)，6.58(1H，d，J＝8Hz)，6.96(1H，dd，J＝8 and 2Hz)，7.28(1H，d，J＝2Hz)，8.06(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/e 362(M+H)⁺

1- (2-chloro-4- (methylthio) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.45(3H，s)，2.65(3H，s)，4.01(3H，s)，5.39(3H，s)，6.42(1H，d，J＝8Hz)，6.98(1H，dd，J＝8 and 2Hz)，7.30(1H，d，J＝2Hz)，7.54(1H，d，J＝8Hz)，8.08(1H，d，J＝8Hz).Mass(ESI)：m/e 362(M+H)⁺Preparation example 80-53- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same method as in preparation example 4-7, methyl 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (146mg) was used to obtain the desired product (184mg) as a white powder.¹H-NMR(DMSO-d₆)：2.45(3H，s)，2.50(3H，s)，5.60(2H，s)，6.44(1H，d，J＝8Hz)，7.10(1H，d，J＝8Hz)，7.42(1H，s)，8.00(1H，d，J＝8Hz)，8.10(1H，d，J＝8Hz).Mass(ESI)：m/e 346(M-H)^-Preparation example 81-13- (2-chloro-4- (methylsulfinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

To a solution of methyl 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (148mg) in dichloromethane (2.8ml) was added m-chloroperbenzoic acid (81mg) under ice-bath conditions, and the mixture was stirred under the same conditions for 1 hour. The reaction mixture was diluted with chloroform, washed with a saturated aqueous sodium bicarbonate solution and saturated brine in this order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, acetonitrile was added to the residue to crystallize it, whereby the desired product (118mg) was obtained as a white powder. ¹H-NMR(CDCl₃)：2.55(3H，s)，2.71(3H，s)，3.99(3H，s)，5.71(2H，s)，6.78(1H，d，J＝8Hz)，7.32(1H，d，J＝8Hz)，7.80(1H，s)，8.09(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz).Mass(ESI)：m/e 378(M+H)⁺Preparation example 81-23- (2-chloro-4- (methylsulfinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- (methylsulfinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (112mg) was used to give the desired product (112mg) as a white powder.¹H-NMR(DMSO-d₆)：2.54(3H，s)，2.76(3H，s)，5.67(2H，s)，6.75(1H，d，J＝8Hz)，7.52(1H，d，J＝8Hz)，7.88(1H，s)，8.01(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz).Mass(ESI)：m/e 362(M-H)^-Preparation example 82-12-chloro-4- (methylsulfonyl) -1- ((methylsulfonyloxy) methyl) benzene

From 2-chloro-4- (methylsulfonyl) benzyl alcohol (457mg) and methanesulfonyl chloride (261mg), the objective product (737mg) was obtained as a white powder in the same manner as in preparation example 14-1.¹H-NMR(DMSO-d₆): 3.31(3H, s), 3.33(3H, s), 5.42(2H, s), 7.85(1H, d, J ═ 8Hz), 7.79(1H, d, J ═ 8Hz), 8.07(1H, s) preparation 82-23- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) and 2-chloro-4- ((methanesulfonyl) -1- ((methanesulfonyloxy) methyl) benzene (344mg), to give white crystals of methyl 3- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (233mg) and methyl 1- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (25 mg).

3- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.56(3H，s)，3.03(3H，s)，3.99(3H，s)，5.72(2H，s)，6.80(1H，d，J＝8Hz)，7.08(1H，d，J＝8Hz)，8.05(1H，s)，8.10(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz).

1- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): preparation of 82-33- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (2H, s), 3.10(3H, s), 4.03(3H, s), 5.62(2H, s), 6.62-6.70(1H, m), 7.75-8.12(4H, m)

According to the same manner as in preparation 4-7, methyl 3- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (236mg) was used to give the desired product as white crystals (199 mg).¹H-NMR(DMSO-d₆): example 83-12-chloro-1- ((methanesulfonyloxy) methyl) -4-nitrobenzene-1H, 2.53(3H, s), 3.25(3H, s), 5.70(2H, s), 6.80(1H, d, J ═ 8Hz), 7.75(1H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz), 8.10(1H, s), 8.13(1H, d, J ═ 8Hz)

According to the same method as in preparation 14-1, from 2-chloro-4-nitrobenzol (2.5g) and methanesulfonyl chloride (1.68g), the objective product (3.56g) was obtained as brown crystals.¹H-NMR(DMSO-d₆): 3.12(3H, s), 5.40(2H, s), 7.73(1H, d, J ═ 8Hz), 8.18(1H, dd, J ═ 2, 8Hz), 8.79(1H, d, J ═ 2Hz), preparation 83-23- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4-nitrobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.00g) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4-nitrobenzene (3.06g), white crystals of methyl 3- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.02g) and pale brown crystals of methyl 1- (2-chloro-4-nitrobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (330mg) were obtained.

3- (2-chloro)-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.55(3H，s)，3.99(3H，s)，5.73(2H，s)，6.80(1H，d，J＝8Hz)，7.97(1H，d，J＝8Hz)，8.08(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz)，8.33(1H，s).

1- (2-chloro-4-nitrobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.65(3H, s), 4.03(3H, s), 5.51(2H, s), 6.62(1H, d, J ═ 8Hz), 7.53(1H, d, J ═ 8Hz), 8.01(1H, dd, J ═ 2,8Hz), 8.10(1H, d, J ═ 8Hz), 8.39(1H, d, J ═ 2Hz), preparation 83-33- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

Methyl 3- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (705mg) was suspended in ethanol (6ml), and reduced iron (437mg) and acetic acid (1.01ml) were added to the suspension, followed by refluxing under heating for 2 hours. Then, reduced iron (218mg) and acetic acid (1.01ml) were added thereto, and the mixture was refluxed for 1 hour. The reaction solution was filtered through celite, the insoluble matter was washed with ethanol, and the filtrate was concentrated under reduced pressure. To the concentrated residue were added an aqueous solution containing sodium hydrogencarbonate and ethyl acetate, and the aqueous layer was made alkaline. At this time, a part of the desired product precipitated, and the precipitate was collected by filtration and the filtrate was separated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and a saturated brine in this order, dried over anhydrous magnesium sulfate, and filtered. The target product precipitated during neutralization was dissolved in methanol/chloroform (1/4) and a solvent, and filtered. The two filtrates were combined and concentrated under reduced pressure to give the desired product (608mg) as a white powder. ¹H-NMR(CDCl₃): 2.53(3H, s), 3.75(2H, s), 4.00(3H, s), 5.67(2H, s), 6.40(1H, dd, J ═ 2,8Hz), 6.54(1H, dd, J ═ 1, 8Hz), 6.72(1H, d, J ═ 1Hz), 8.02(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), preparation 83-43- (4- (benzylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (100mg) was dissolvedAfter dissolving in methanol (1ml), benzaldehyde (39mg), zinc chloride (49mg) and sodium cyanoborohydride (23mg) were added. After stirring at room temperature for 2 hours, the mixture was refluxed for 15 minutes. Benzaldehyde (16mg), zinc chloride (21mg) and sodium cyanoborohydride (10mg) were then added to the solution, and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added ice water, followed by saturated aqueous sodium bicarbonate solution. The product was extracted with ethyl acetate, and the organic layer was washed successively with a saturated aqueous sodium bicarbonate solution and a saturated brine. Anhydrous magnesium sulfate was added, dried and filtered. The filtrate was concentrated under reduced pressure, hexane was added to the residue, and the precipitated yellow crystals were washed, collected by filtration, and dried under reduced pressure to give the objective product (120 mg).¹H-NMR(CDCl₃): 2.52(3H, s), 3.98(3H, s), 4.17(1H, t, J ═ 7Hz), 4.27(2H, d, J ═ 6Hz), 5.56(2H, s), 6.34(1H, dd, J ═ 2,8Hz), 6.55(1H, d, J ═ 8Hz), 6.66(1H, d, J ═ 2Hz), 7.25 to 7.37(5H, m), 8.02(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), preparation 83-53- (4- (benzylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4- (benzylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (103mg) was used to obtain the desired product (82mg) as white crystals.¹H-NMR(DMSO-d₆): preparation of 84-13- (4- (n-butylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (1H, 2-chlorobenzyl) in example 84-13- (4- (n-butylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] acid methyl ester

According to the same manner as in preparation 84-4, methyl 3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (100mg) and n-butyraldehyde (37mg) were used to obtain the desired product (87mg) as pale yellow crystals.¹H-NMR(CDCl₃)：0.93(3H，t，J＝8Hz)，1.37-1.48(2H，m)，1.52-1.62(2H，m)，2.55(3H，s)，4.00(2H，q，J＝7Hz)，3.72(1H，br s)，4.01(3H，s)，5.57(2H，s)，6.32(1H，dd，J＝2，8Hz)，6.57(1H，d，J＝8Hz)，6.60(1H, d, J ═ 2Hz), 8.02(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), preparation 84-23- (4- (n-butylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same method as in preparation example 4-7, methyl 3- (4- (n-butylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (75mg) was used to give the desired product (54mg) as white crystals. ¹H-NMR(DMSO-d₆): 0.88(3H, t, J ═ 8Hz), 1.23-1.40(2H, m), 1.42-1.53(2H, m), 2.49(3H, s), 2.92(2H, q, J ═ 7Hz), 5.45(2H, s), 5.93(1H, t, J ═ 7Hz), 6.38(1H, d, J ═ 8Hz), 6.44(1H, d, J ═ 8Hz), 6.63(1H, s), 8.00(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), preparation example 85-13- (2-chloro-4- (N, N-dimethylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

Methyl 3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (100mg) was dissolved in acetonitrile (1ml), and 37% formaldehyde solution (0.123ml) and sodium cyanoborohydride (29mg) were added to stir at room temperature for 1 hour. Then, 37% formaldehyde solution (0.123ml) and sodium cyanoborohydride (29mg) were added thereto, and the reaction mixture was made neutral by adding acetic acid and stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and ice water and then a saturated aqueous sodium bicarbonate solution were added to the residue. The product was extracted with ethyl acetate, and the organic layer was washed successively with aqueous sodium hydrogencarbonate solution and saturated brine. Anhydrous magnesium sulfate was added, dried and filtered. The filtrate was concentrated under reduced pressure, hexane was added to the residue, and the precipitated yellow crystals were washed, collected by filtration, and dried under reduced pressure to give the objective product (97 mg). ¹H-NMR(CDCl₃): 2.52(3H, s), 2.90(6H, s), 4.00(3H, s), 5.59(2H, s), 6.42(1H, dd, J ═ 2,8Hz), 6.62(1H, d, J ═ 8Hz), 6.70(1H, d, J ═ 2Hz), 8.03(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz), preparation 85-23- (2-chloro-4- (N, N-dimethylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

By the same method as in production examples 4 to 7, from 3- (2-chloro-4- (N, N-dimethylamino) benzyl) -2-methylMethyl (90mg) 3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate gave the desired product as white crystals (65 mg).¹H-NMR(DMSO-d₆): preparation of 86-13- (4- (acetylamino) -2-chlorobenzyl) -2-methyl-3H- [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester 2.50(3H, s), 2.87(6H, s), 5.48(2H, s), 6.78(1H, s), 7.98(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz)

Methyl 3- (4-amino-2-chloro-benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (150mg) was dissolved in 1, 2-dichloroethane (1.5ml), and acetic anhydride (148mg) and acetic acid (87mg) were added thereto at room temperature, followed by heating and refluxing for 1 hour. The reaction mixture was concentrated under reduced pressure, and ice water and then a saturated aqueous solution of sodium hydrogencarbonate were added to the residue to collect precipitated white crystals by filtration, which were washed with water and dried under reduced pressure to obtain the desired product (139 mg). ¹H-NMR(CDCl₃): 2.12(3H, s), 2.52(3H, s), 3.40(1H, s), 3.99(3H, s), 5.60(2H, s), 6.51(1H, d, J ═ 8Hz), 7.13(1H, d, J ═ 8Hz), 7.83(1H, s), 8.05(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz), preparation 86-23- (4- (acetylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4- (acetylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (123mg) was used to obtain the desired product (116mg) as white crystals.¹H-NMR(DMSO-d₆): example 87-13- (2-chloro-4- (methylsulfonylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester was prepared 2.03(3H, s), 2.50(3H, s), 5.55(2H, s), 6.57(1H, d, J ═ 8Hz), 7.23(1H, d, J ═ 8Hz), 7.95(1H, s), 7.98(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz)

Methyl 3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (150mg) was dissolved in (1.5ml), and a pyridine (0.5ml) solution of methanesulfonyl chloride (114mg) was added thereto at room temperature, followed by refluxing under heating for 1 hour. Then, a solution of methanesulfonyl chloride (114mg) in pyridine (0.5ml) was added thereto at room temperature, and the mixture was left at room temperature overnight. The reaction solution was concentrated under reduced pressure, and ice water was added to the residue The product was extracted with chloroform. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and a saturated brine in this order, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and ethanol was added to the residue to wash the crystals, which were collected by filtration and dried under reduced pressure to give the objective product (101mg) as pale yellow crystals.¹H-NMR(CDCl₃): 2.52(3H, s), 3.04(3H, s), 3.97(3H, s), 5.60(2H, s), 6.10(1H, d, J ═ 8Hz), 6.90(1H, d, J ═ 8Hz), 7.20(1H, d, J ═ 3Hz), 8.07(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz), 8.87(1H, s), preparation 87-23- (2-chloro-4- (methylsulfonylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- (2-chloro-4- (methylsulfonylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (92mg) was used to give the desired product as pale yellow crystals (88 mg).¹H-NMR(DMSO-d₆): example 883- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid was prepared 2.48(3H, s), 3.01(3H, s), 5.55(2H, s), 6.60(1H, d, J ═ 8Hz), 7.03(1H, d, J ═ 8Hz), 7.33(1H, s), 7.97(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz)

According to the same manner as in preparation 4-7, methyl 3- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (300mg) was used to obtain the desired product (258mg) as white crystals. ¹H-NMR(DMSO-d₆): 2.52(3H, s), 5.70(2H, s), 6.82(1H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz), 8.04(1H, dd, J ═ 2, 8Hz), 8.12(1H, d, J ═ 8Hz), 8.40(1H, s), preparation 89-13-chloro-4- (hydroxymethyl) benzaldehyde

The desired product (112mg) was obtained as a pale yellow powder from 4- ((tert-butyldimethylsiloxy) methyl) -3-chlorobenzaldehyde (228mg) in the same manner as in preparation example 70-3.¹H-NMR(CDCl₃): 2.04(1H, br, s), 4.88(2H, br, s), 7.76(1H, d, J ═ 8Hz), 7.82(1H, d, J ═ 8Hz), 7.88(1H, s), 9.98(1H, s), preparation 89-23-chloro-4- ((methanesulfonyloxy) methyl) benzaldehyde

The desired product (577mg) was obtained as a pale yellow oil by the same method as in preparation example 14-1 from 3-chloro-4- (hydroxymethyl) benzaldehyde (393 mg).¹H-NMR(CDCl₃): 3.12(3H, s), 5.40(2H, s), 7.72(1H, d, J ═ 8Hz), 7.84(1H, d, J ═ 8Hz), 7.94(1H, s), 9.98(1H, s). preparation of 89-33- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4-formylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.60g) and 3-chloro-4- ((methanesulfonyloxy) methyl) benzaldehyde (3.72g), colorless crystals of methyl 3- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.71g) and amorphous methyl 1- (2-chloro-4-formylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.40g) were obtained. 3- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo (4, 5-b) pyridine-5-carboxylic acid methyl ester ¹H-NMR(CDCl₃)：2.54(3H，s)，3.99(3H，s)，5.73(2H，s)，6.77(1H，d，J＝8Hz)，7.61(1H，d，J＝8Hz)，7.98(1H，s)，8.10(1H，d，J＝8Hz)，8.18(1H，d，J＝8Hz)，9.94(1H，s)Mass(ESI)：m/z 344(M+1)mp 189-191℃

1- (2-chloro-4-formylbenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.64(3H, s), 4.00(3H, s), 5.50(2H, s), 6.61(1H, d, J ═ 8Hz), 7.55(1H, d, J ═ 8Hz), 7.64(1H, br d, J ═ 8Hz), 8.00(1H, s), 8.09(1H, d, J ═ 8Hz), 8.18(1H, d, J ═ 8Hz), 9.95(1H, s) mass (esi): m/z 344(M +1) preparation 89-43- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, from methyl 3- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg), the desired product (202mg) was obtained as colorless crystals.¹H-NMR(DMSO-d₆)：2.53(3H，s)，5.70(2H，s)，6.78(1H, d, J ═ 8Hz), 7.75(1H, d, J ═ 8Hz), 8.01(1H, d, J ═ 8Hz), 8.09(1H, s), 8.16(1H, d, J ═ 8Hz), 9.96(1H, s) mass (esi): m/z 328(M-1) mp 188-

A suspension of methyl 3- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg, 0.582mmol), thiazolidine-2, 4-dione (82mg, 0.698mmol) and piperidine (25mg, 0.291mmol) in ethanol (4ml) was heated under reflux overnight. After the reaction solution was cooled, the precipitated crystals were collected by filtration to obtain the objective product (189mg) as pale yellow crystals. ¹H-NMR(DMSO-d₆): 2.54(3H, s), 3.85(3H, s), 5.64(2H, s), 6.71(1H, d, J ═ 8Hz), 7.42(1H, d, J ═ 8Hz), 7.74(1H, s), 7.82(1H, s), 8.02(1H, d, J ═ 8Hz), 8.17(1H, d, J ═ 8Hz), mass (esi): m/z 441(M-1) mp > 300 deg.C preparation 90-23- [ 2-chloro-4- [ (2, 4-dioxo-1, 3-thiazolidin-5-ylidene) methyl ] benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, from methyl 3- [ 2-chloro-4- [ (thiazolidine-2, 4-diketo-5-ylidene) methyl ] benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (80mg), the desired product (63mg) was obtained as colorless crystals.¹H-NMR(DMSO-d₆): 2.51(3H, s), 5.67(2H, s), 6.70(1H, d, J ═ 8Hz), 7.42(1H, d, J ═ 8Hz), 7.75(1H, s), 7.84(1H, s), 8.01(1H, d, J ═ 8Hz), 8.16(1H, d, J ═ 8Hz) mass (esi): m/z 427(M-1) mp > 300 deg.C preparation 91-12-chloro-4-fluorobenzyl alcohol

From 2-chloro-4-fluorobenzoic acid (5.00g), a white crystalline desired product (4.20g) was obtained in the same manner as in 74-4.¹H-NMR(CDCl₃): 1.92(1H, br s), 4.75(2H, br d), 6.99(1H, dt, J ═ 2, 8Hz), 7.12(1H, dd, J ═ 2, 8Hz), 7.47(1H, t, J ═ 7Hz), preparation 91-22-chloro-4-fluoro-1- ((methanesulfonyloxy) methyl) benzene

According to the same phase as that of preparation example 14-1The same procedure, from 2-chloro-4-fluorobenzyl alcohol (400mg) and methanesulfonyl chloride (314mg), gave the objective product (572mg) as a colorless oil.¹H-NMR(CDCl₃): 3.02(3H, s), 5.30(2H, s), 7.03(1H, dt, J ═ 2, 8Hz), 7.20(1H, dd, J ═ 2, 8Hz), 7.49(1H, t, J ═ 8Hz), preparation examples 91-33- (2-chloro-4-fluorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4-fluorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (150mg) and 2-chloro-4-fluoro-1- ((methanesulfonyloxy) methyl) benzene (206mg), white crystalline 3- (2-chloro-4-fluorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (100mg) and pale yellow crystalline 1- (2-chloro-4-fluorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (55mg) were obtained.

3- (2-chloro-4-fluorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.53(3H，s)，4.00(3H，s)，5.62(2H，s)，6.70(1H，dt，J＝1,8Hz)，6.85(1H，dt，J＝2，8Hz)，7.20(1H，dd，J＝2，8Hz)，8.05(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz).

1- (2-chloro-4-fluorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.65(3H, s), 4.02(3H, s), 5.40(2H, s), 6.50(1H, dt, J ═ 1, 8Hz), 6.87(1H, dt, J ═ 2, 8Hz), 7.23(1H, dd, J ═ 2, 8Hz), 7.53(1H, d, J ═ 8Hz), 8.08(1H, d, J ═ 8Hz), preparation 91-43- (2-chloro-4-fluorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4-fluorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (90mg) was used to give the desired product (75mg) as white crystals.¹H-NMR(DMSO-d₆)：2.51(3H，s)，5.59(2H，s)，6.67(1H，dt，J＝1，8Hz)，7.11(1H，dt，J＝1，8Hz)，7.60(1H，dd，J＝2，8Hz)，8.01(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz)

The same procedures used in preparation 74-4 were repeated except for using 2, 4, 6-trichlorobenzoic acid (5.00g) to give the desired product (4.14g) as white crystals.¹H-NMR(CDCl₃): 2.04(1H, br s), 4.91(2H, s), 7.36(2H, s) -preparation 92-22, 4, 6-trichloro-1- ((methylsulfonyloxy) methyl) benzene

The desired product (407mg) was obtained as white crystals from 2, 4, 6-trichlorophenylmethanol (300mg) and methanesulfonyl chloride (179mg) according to the same method as in preparation example 14-1.¹H-NMR(CDCl₃): 3.08(3H, s), 5.48(2H, s), 7.42(2H, s.) preparation 92-32-methyl-3- (2, 4, 6-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 2-methyl-1- (2, 4, 6-trichlorophenylmethyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (150mg) and 2, 4, 6-trichloro-1- ((methanesulfonyloxy) methyl) benzene (250mg), white crystalline 2-methyl-3- (2, 4, 6-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (129mg) and pale yellow crystalline 2-methyl-1- (2, 4, 6-trichlorophenylmethyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (100mg) were obtained.

2-methyl-3- (2, 4, 6-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.46(3H，s)，4.00(3H，s)，5.79(2H，s)，7.39(2H，s)，7.97(1H，d，J＝1，8Hz)，8.07(1H，d，J＝1，8Hz).

2-methyl-1- (2, 4, 6-trichlorophenylmethyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): preparation 92-42-methyl-3- (2, 4, 6-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (2.73 (3H, s), 4.00(3H, s), 5.56(2H, s), 7.34(1H, d, J ═ 8Hz), 7.44(2H, s), 7.98(1H, d, J ═ 8Hz)

According to the same manner as in preparation examples 4-7In the same manner, methyl 2-methyl-3- (2, 4, 6-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (94mg) was used to give the desired product (83mg) as white crystals.¹H-NMR(DMSO-d₆): 2.50(3H, s), 5.71(2H, s), 7.72(2H, s), 7.92(1H, d, J ═ 8Hz), 8.03(1H, d, J ═ 8Hz)

2, 3, 4-trichlorotoluene (2.00g) was dissolved in carbon tetrachloride (20ml), and 2, 2' -azobis (2, 4-dimethyl-4-methoxyvaleronitrile) (158mg) and N-bromosuccinimide (2.00g) were added. After heating and refluxing for 2 hours, hexane (20ml) was added thereto, and the mixture was stirred for 30 minutes while cooling with ice. After filtration, the insoluble matter on the filter paper was washed with a small amount of hexane, and the filtrates were combined and concentrated under reduced pressure. To the residue was added diisopropyl ether, and the mixture was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine in this order, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give a mixture (2.40g) of the desired product as brown crystals and 2, 3, 4-trichlorotoluene. ¹H-NMR(CDCl₃): 4.57(2H, s), 7.29(1H, d, J. 8Hz), 7.37(1H, d, J. 8 Hz.) preparation 93-22-methyl-3- (2, 3, 4-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 2-methyl-1- (2, 3, 4-trichlorophenylmethyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) and brominated 2, 3, 4-trichlorophenylmethyl (1.44g), white crystalline methyl 2-methyl-3- (2, 3, 4-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (196mg) and pale brown crystalline methyl 2-methyl-1- (2, 3, 4-trichlorophenylmethyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (82mg) were obtained.

2-methyl-3- (2, 3, 4-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.54(3H，s)，3.98(3H，s)，5.65(2H，s)，6.43(1H，d，J＝8Hz)，7.23(1H，d，J＝9Hz)，8.07(1H，d，J＝8Hz)，8.15(1H，d，J＝8Hz).

2-first1- (2, 3, 4-Trichlorophenylmethyl) -1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.65(3H, s), 4.03(3H, s), 5.42(2H, s), 6.26(1H, d, J ═ 8Hz), 7.26(1H, d, J ═ 8Hz), 7.53(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), preparation 93-32-methyl-3- (2, 3, 4-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 2-methyl-3- (2, 3, 4-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (185mg) was used to give the desired product (156mg) as white crystals.¹H-NMR(DMSO-d₆): 2.53(3H, s), 5.62(2H, s), 6.52(1H, d, J ═ 8Hz), 7.52(1H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz), preparation 94-12, 4-dichloro-5-fluorobenzyl alcohol

The same procedures used in preparation 74-4 were repeated except for using 2, 4-dichloro-5-fluorobenzoic acid (1.25g) to give the desired product (1.00g) as white crystals.¹H-NMR(CDCl₃): 1.96(1H, t, J ═ 7Hz), 4.73(2H, d, J ═ 7Hz), 7.35(1H, d, J ═ 9Hz), 7.40(1H, d, J ═ 7Hz), preparation 94-22, 4-dichloro-5-fluoro-1- ((methanesulfonyloxy) methyl) benzene

The same procedure as in preparation 14-1 was followed to give the desired product (404mg) from 2, 4-dichloro-5-fluorobenzyl alcohol (300mg) and methanesulfonyl chloride (194mg) as a colorless oil.¹H-NMR(CDCl₃): 3.08(3H, s), 5.27(2H, s), 7.32(1H, d, J ═ 9Hz), 7.49(1H, d, J ═ 7Hz), preparation of methyl 94-33- (2, 4-dichloro-5-fluorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate and methyl 1- (2, 4-dichloro-5-fluorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate

According to the same manner as in preparation example 14-2, from 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (200mg) and 2, 4-dichloro-5-fluoro-1 ((methanesulfonyloxy) methyl) benzene (314mg), white crystalline 3- (2, 4-dichloro-5-fluorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (234mg) and pale yellow crystalline 1- (2, 4-dichloro-5-fluorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (86mg) were obtained.

3- (2, 4-dichloro-5-fluorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.57(3H，s)，4.00(3H，s)，5.60(2H，s)，6.53(1H，d，J＝9Hz)，7.52(1H，d，J＝8Hz)，8.08(1H，d，J＝8Hz)，8.17(1H，d，J＝8Hz).

1- (2, 4-dichloro-5-fluorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.67(3H, s), 4.03(3H, s), 5.38(2H, s), 6.28(1H, d, J ═ 9Hz), 7.55(1H, d, J ═ 8Hz), 7.56(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), preparation 94-43- (2, 4-dichloro-5-fluorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- (2, 4-dichloro-5-fluorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (215mg) was used to give the desired product (198mg) as white crystals.¹H-NMR(DMSO-d₆): 2.55(3H, s), 5.58(2H, s), 6.82(1H, d, J ═ 9Hz), 7.95(1H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz), 8.12(1H, dd, J ═ 1,8Hz), preparation 95-12-chloro-4-iodobenzyl bromide

The same procedures used in preparation 93-1 were repeated except for using 2-chloro-4-iodotoluene (5.10g) to give the desired product (5.83g) as a pale yellow oil.¹H-NMR(CDCl₃): 4.52(2H, s), 7.17(1H, d, J. 8Hz), 7.60(1H, d, J. 8Hz), 7.76(1H, s) preparation 95-23- (2-chloro-4-iodobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4-iodobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (150mg) and 2-chloro-4-iodobenzyl bromide (780mg), methyl 3- (2-chloro-4-iodobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (163mg) and methyl 1- (2-chloro-4-iodobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (108mg) were obtained as pale brown powders.

3- (2-chloro-4-iodobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.54(3H，s)，3.99(3H，s)，5.62(2H，s)，6.37(1H，d，J＝8Hz)，7.43(1H，d，J＝8Hz)，7.80(1H，s)，8.08(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz).

1- (2-chloro-4-iodobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): example 95-33- (2-chloro-4-iodobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid preparation (1H, s), 4.03(3H, s), 5.38(2H, s), 6.20(1H, d, J ═ 8Hz), 7.48(1H, d, J ═ 8Hz), 7.53(1H, d, J ═ 8Hz), 7.83((1H, s), 8.09(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4-iodobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (160mg) was used to give the desired product (115mg) as a white powder.¹H-NMR(DMSO-d₆): 2.50(3H, s), 5.57(2H, s), 6.34(1H, d, J ═ 8Hz), 7.60(1H, d, J ═ 8Hz), 7.97(1H, s), 8.02(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), preparation 96-12, 5-dichloro-3- (hydroxymethyl) thiophene

The desired product (718mg) was obtained as a pale yellow oil by the same method as in preparation example 76-2, starting from methyl 2, 5-dichlorothiophene-3-carboxylate (835 mg).¹H-NMR(CDCl₃): 1.70(1H, t, J ═ 6Hz), 4.58(2H, d, J ═ 6Hz), 6.88(1H, s). preparation 96-22, 5-dichloro-3- ((methanesulfonyloxy) methyl) thiophene

The same procedures used in preparation example 14-1 were repeated except for using 2, 5-dichloro-3- (hydroxymethyl) thiophene (300mg) and methanesulfonyl chloride (206mg) to give the desired product (384mg) as a colorless oil.¹H-NMR(CDCl₃): 3.02(3H, s), 5.12(2H, s), 6.90(1H, s). preparation 96-33- ((2, 5-dichlorothien-3 yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- ((2, 5-dichlorothien-3-yl) methyl) -2-methyl-1H-imidAzolo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (150mg) and 2, 5-dichloro-3- ((methanesulfonyloxy) methyl) thiophene (225mg), white crystalline 3- ((2, 5-dichlorothien-3 yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (87mg), pale yellow crystalline 1- ((2, 5-dichlorothien-3-yl) methyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (59mg) was obtained.

3- ((2, 5-Dichlorothiophen-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.64(3H，s)，4.03(3H，s)，5.42(2H，s)，6.66(1H，s)，8.02(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).

1- ((2, 5-Dichlorothiophen-3-yl) methyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): preparation 96-43- ((2, 5-dichlorothien-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid, 6.30(1H, s), 4.02(3H, s), 5.20(2H, s), 6.30(1H, s), 7.64(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 4-7, methyl 3- ((2, 5-dichlorothien-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (77mg) gave the desired product (67mg) as white crystals.¹H-NMR(DMSO-d₆): 2.60(3H, s), 5.43(2H, s), 6.94(1H, s), 7.99(1H, d, J ═ 8Hz), 8.07(1H, d, J ═ 8Hz) preparation of 97-13- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) and 6-chloropiperidyl chloride (236mg), methyl 3- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (169mg) and methyl 1- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (75mg) were obtained as white crystals.

3- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.56(3H，s)，4.00(3H，s)，5.59(2H，s)，5.91(2H，s)，6.23(1H，s)，6.89(1H，s)，8.04(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz).

1- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.67(3H, s), 4.02(3H, s), 5.33(2H.s), 5.94(2H, s), 5.99(1H, s), 6.92(1H, s), 7.57(1H, d, J ═ 8Hz), 8.08(1H, d, J ═ 8Hz), preparation 97-23- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (160mg) gave the desired product (144mg) as yellow crystals.¹H-NMR(DMSO-d₆): 2.46(3H, s), 5.47(2H, s), 6.00(2H, s), 6.11(1H, s), 7.19(1H, s), 7.88(1H, d, J ═ 8Hz), 7.92(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 14-1, from 2-chloro-3- (hydroxymethyl) quinoline (300mg) and methanesulfonyl chloride (89mg), a mixture of 2-chloro-3- ((methanesulfonyloxy) methyl) quinoline and 2-chloro-3- (chloromethyl) quinoline (377mg) was obtained as a pale yellow powder. This material was used in the following reaction without purification. Preparation examples 98-23- ((2-chloroquinolin-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- ((2-chloroquinolin-3-yl) methyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) and 2-chloro-3- ((methanesulfonyloxy) methyl) quinoline (313mg, a mixture with 2-chloro-3- (chloromethyl) quinoline), to give pale yellow crystals of methyl 3- ((2-chloroquinolin-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (112mg) and pale yellow crystals of methyl 1- ((2-chloroquinolin-3-yl) methyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (100 mg).

3- ((2-Chloroquinolin-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.63(3H，s)，3.97(3H，s)，5.80(2H，s)，7.39(1H，s)，7.50(1H，t，J＝7Hz)，7.58(1H，d，J＝8Hz)，7.72(1H，t，J＝8Hz)，8.03(1H，d，J＝8Hz)，8.12(1H，d，J＝8Hz)，8.18(1H，dd，J＝1，8Hz).

1- ((2-Chloroquinolin-3-yl) methyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.70(3H, s), 4.03(3H, s), 5.59(2H, s), 7.10(1H, s), 7.49-7.62(3H, m), 7.70-7.78(1H, m), 8.02-8.20(2H, m). preparation 98-33- ((2-chloroquinolin-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- ((2-chloroquinolin-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (100mg) gave the desired product (90mg) as white crystals.¹H-NMR(DMSO-d₆): examples of preparation of 99-13- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester are 2.60(3H, s), 5.74(2H, s), 7.58(1H, t, J ═ 7Hz), 7.70(1H, s), 7.80(1H, t, J ═ 8Hz), 7.91(1H, d, J ═ 8Hz), 8.00(2H, t, J ═ 8Hz), 8.16(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (150mg) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4- (trifluoromethyl) benzene (262mg), to give white crystals of methyl 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (129mg) and methyl 1- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (129 mg).

3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.54(3H，s)，3.99(3H，s)，5.71(2H，s)，6.73(1H，d，J＝8Hz)，7.38(1H，d，J＝8Hz)，7.72(1H，s)，8.08(1H，d，J＝8Hz)，8.17(1H，d，J＝8Hz).

1- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): preparation of 99-23- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] -5-carboxylic acid (3H, s), 4.03(3H, s), 5.49(2H, s), 6.57(1H, d, J ═ 8Hz), 7.40(1H, d, J ═ 8Hz), 7.53(1H, d, J ═ 8Hz), 7.76(1H, s), 8.10(1H, d, J ═ 8Hz)

According to the same manner as in preparation 4-7, methyl 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (119mg) was used to obtain the desired product (103mg) as white crystals.¹H-NMR(DMSO-d₆): 2.53(3H, s), 5.69(2H, s), 6.75(1H, d, J ═ 8Hz), 7.60(1H, d, J ═ 8Hz), 8.02(1H, d, J ═ 8Hz), 8.03(1H, s), 8.15(1H, d, J ═ 8Hz), preparation examples 100-13- (1-bromonaphthalen-2-ylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (1-bromonaphthalen-2-ylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (150mg) and 1-bromonaphthalen-2-ylmethyl bromide (259mg), white crystalline methyl 3- (1-bromonaphthalen-2-ylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1122mg), methyl 1- (1-bromonaphthalen-2-ylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (198mg) was obtained.

3- (1-Bromnaphthol-2-ylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.50(3H，s)，3.97(3H，s)，5.92(2H，s)，6.65(1H，d，J＝8Hz)，7.56(1H，t，J＝8Hz)，7.64(2H，dt，J＝1.8Hz)，7.77(1H，d，J＝8Hz)，8.08(1H，d，J＝8Hz)，8.17(1H，d，J＝8Hz)，8.37(1H，d，J＝8Hz).

1- (1-Bromnaphthol-2-ylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.68(3H, s), 4.02(3H, s), 5.67(2H, s), 6.52(1H, d, J ═ 8Hz), 7.53-7.60(2H, m), 7.68(2H, dt, J ═ 2.7Hz), 7.81(1H, d), 8.07(1H, d), 8.36(1H, d, J ═ 7Hz), preparation 100-23- (1-bromonaphthalen-2-ylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- (1-bromonaphthalen-2-ylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (105mg) was used to obtain the desired product (81mg) as white crystals.¹H-NMR(DMSO-d₆): 2.51(3H, s), 5.83(2H, s), 6.62(1H, d, J ═ 8Hz), 7.62(1H, t, J ═ 8Hz), 7.75(1H, t, J ═ 8Hz), 7.86(1H, d, J ═ 8Hz), 7.96(1H, d, J ═ 8Hz), 8.03(1H, d, J ═ 8Hz), 7.17(1H, d, J ═ 8Hz), 8.31(1H, d, J ═ 8Hz), preparation of example 1013- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- (4-bromo-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methylimidazo [ 4, 5-b ] pyridine-5-carboxylate (400mg) and 4-bromo-2-chloro-1- ((methanesulfonyloxy) methyl) benzene (689mg), methyl 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (400mg) was obtained as a white powder and methyl 1- (4-bromo-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (250mg) as a pale yellow powder.

3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.54(3H，s)，4.00(3H，s)，5.62(2H，s)，6.53(1H，d，J＝8Hz)，7.25(1H，d，J＝8Hz)，7.61(1H，s)，8.08(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz).Mass(ESI)：m/z 396(M+1)

1- (4-bromo-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.64(3H, s), 4.01(3H, s), 5.49(2H, s), 6.36(1H, d, J ═ 8Hz), 7.29(1H, d, J ═ 8Hz), 7.53(1H, d, J ═ 8Hz), 7.65(1H, s), 8.09(1H, d, J ═ 8Hz) mass (esi): m/z 396(M +1) preparation 102-12, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine-4-oxide

To a chloroform (43ml) solution of 2, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine (4.29g) was added m-chloroperbenzoic acid (80%, 7.55g) at room temperature, and the mixture was refluxed for 1 hour. After cooling to room temperature, the reaction mixture was purified directly by silica gel column chromatography (chloroform/methanol 9/1), and the extract was further pulverized with ethyl acetate to give the desired product (4.16g) as a brown powder. ¹H-NMR(DMSO-d₆): preparation of 102-25-chloro-2, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine (3H, s), 2.52(3H, s), 6.93(1H, d, J ═ 5Hz), 7.98(1H, d, J ═ 5Hz)

A mixture of 2, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine-4-oxide (4.45g) in chloroform (4.5ml) and phosphorus oxychloride (25.4ml) was stirred at 80 ℃ for 3 hours, and then concentrated and dried under reduced pressure to solidify. The residue was poured into ice (75g), and neutralized with aqueous ammonia under ice bath conditions. After stirring at room temperature for 30 minutes, the precipitated solid was collected by filtration and washed with water to give the desired product (3.66g) as a gray powder.¹H-NMR(DMSO-d₆): 2.49(3H, s), 2.52(3H, s), 7.08(1H, s.) preparation 102-35-bromo-2, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine

The same procedures used in preparation 9-1 were repeated except for using 6-chloro-2, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine (3.6g) to give the desired product (4.07g) as a brown solid.¹H-NMR(DMSO-d₆)：2.44-2.57(6H，overlapped with DMSO-d₆) 7.20(1H, s). Mass (ESI): m/z 226(M-1) preparation 102-42, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 110-4 described below, from 5-bromo-2, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine (4.02g), the desired product (2.44g) was obtained as a white powder. ¹H-NMR(CDCl₃)：2.72(3H，s)，2.80(3H，s)，3.49(1H，brs)，4.02(3H，s)，7.91(1H，s).Mass(ESI)：m/e 206(M+1)⁺Preparation example 102-53- (1-Bromnaphthol-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

Sodium hydride (70% in mineral oil, 125mg) was added to a suspension of methyl 2, 7-dimethyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (625mg) in N, N-dimethylformamide (6ml) under ice-bath conditions, and the mixture was stirred for 30 minutes. To the reaction mixture was added brominated 1-bromonaphthalen-2-ylmethyl group (1.05g), and the mixture was stirred under ice-cold-water conditions for 3 hours. Diisopropyl ether (12ml) was added to the reaction mixture, and the precipitate was collected by filtration to give the desired product (1.35g) as a white powder.¹H-NMR(CDCl₃)：2.49(3H，s)，2.75(3H，s)，3.98(3H，s)，5.91(2H，s)，6.64(1H，d，J＝8Hz)，7.49-7.83(4H，m)，8.00(1H，s)，8.38(1H，d，J＝8Hz).Mass(ESI)：m/e 426(M+1)⁺Preparation example 102-63- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.34g) was used to obtain the desired product (1.01g) as a white powder.¹H-NMR(DMSO-d₆)：2.49(3H，s)，2.62(3H，s)，5.82(2H，s)，6.53(1H，d，J＝8Hz)，7.55-8.00(5H，m)，8.29(1H，d，J＝8Hz).Mass(ESI)：m/e 408.410(M-1)^-Preparation 103-13- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 102-6, methyl 2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (550mg) and 4-bromo-2-chloro-1- ((methanesulfonyloxy) methyl) benzene (963mg) were used to give the desired product (950mg) as colorless crystals. ¹H-NMR(CDCl₃)：2.52(3H，s)，2.73(3H，s)3.98(3H, s), 5.59(2H, s), 6.49(1H, d, J ═ 8Hz), 7.22(1H, d, J ═ 8Hz), 7.60(1H, s), 7.99(1H, d, J ═ 8Hz), preparation 103-23- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (950mg) was used to give the desired product (870mg) as colorless crystals.¹H-NMR(DMSO-d₆): preparation of example 1043- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester 2.49(3H, s), 2.62(3H, s), 5.55(2H, s), 6.47(1H, d, J ═ 8Hz), 7.43(1H, dd, J ═ 8, 1Hz), 7.85(1H, d, J ═ 1Hz)

The desired product was obtained as a pale yellow powder from 5-bromo-3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine in the same manner as in preparation 26-2.¹H-NMR(CDCl₃)：2.53(3H，s)，3.99(3H，s)，5.63(2H，s)，6.60(1H，d，J＝8Hz)，7.10(1H，dd，J＝8 and 2Hz)，7.47(1H，d，J＝2Hz)，8.07(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz).Mass(ESI)：m/e 350(M+H)⁺Preparation 105-13- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 102-6, from methyl 2, 7-dimethylimidazo [ 4, 5-b ] pyridine-5-carboxylate (500mg) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4-nitrobenzene (777mg), the desired product (759mg) was obtained as a pale brown powder. ¹H-NMR(CDCl₃): 2.54(3H, s), 2.65(3H, s), 3.83(3H, s), 5.68(2H, s), 6.82(1H, d, J ═ 8Hz), 7.90(1H, s), 8.08(1H, dd, J ═ 8.2Hz), 8.42(1H, d, J ═ 2Hz), preparation 105-23- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

The desired product was obtained as a pale brown powder from methyl 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (755mg) according to the same process as in preparation examples 4 to 7(681mg)。¹H-NMR(DMSO-d₆): 2.52(3H, s), 2.62(3H, s), 5.69(2H, s), 6.77(1H, d, J ═ 8Hz), 7.85(1H, s), 8.05(1H, dd, J ═ 8.2Hz), 8.40(1H, d, J ═ 2Hz), preparation 106-12-amino 6-bromo-3-nitropyridine

To a suspension of 2, 6-dibromo-3-nitropyridine (5.00g) in ethanol (10ml) was added an ammonia/ethanol solution (6.8M, 15ml) at room temperature, and the reaction vessel was closed and stirred at room temperature for 19 hours. Water (25ml) was added to the reaction mixture, and the precipitate was collected by filtration and washed with ethanol. This was suspended in ethanol (55ml), heated, cooled, and filtered to collect the precipitate, thereby obtaining the desired product (3.19g) as a yellow powder.¹H-NMR(DMSO-d₆)：6.89(1H，d，J＝8Hz)，8.24(1H，d，J＝8Hz)，8.25(2H，brs).Mass(ESI)：m/e 216.218(M-H)^-Preparation example 106-22- (acetylamino) -6-bromo-3-nitropyridine

Acetic anhydride (48ml) and sulfuric acid (2.9ml) were added to a suspension of 2-amino-6-bromo-3-nitropyridine (23.9g) in acetic acid (48ml), and the mixture was heated at 65 ℃ for 40 minutes, whereupon the product precipitated as soon as it was homogeneous, forming a suspension. The reaction mixture was allowed to cool, poured into cold water (480ml), and stirred for 30 minutes. The precipitate was collected by filtration and washed with water to give the crude product. This was suspended in diethyl ether (60ml) and collected by filtration to give the desired product (27.2g) as a pale yellow powder. ¹H-NMR(CDCl₃)：2.54(3H，s)，7.33(1H，d，J＝8Hz)，8.33(1H，d，J＝8Hz)，9.95(1H，brs).Mass(ESI)：m/e 258，260(M-H)^-Preparation 106-36-bromo-2- (N- (2-chloro-4-cyanophenylmethyl) acetylamino) -3-nitropyridine

2- (acetylamino) -6-bromo-3-nitropyridine (3.21g) was dissolved in dry N, N-dimethylformamide (16ml), and sodium hydride (in 60% oil, 326mg) cooled with ice was added to stir for 30 minutes. A solution of 2-chloro-4-cyanobenzyl bromide (2.34g) in dry N, N-dimethylformamide (4ml) was added dropwise at the same temperature, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into ice-water, followed by extraction with ethyl acetate. Drying the organic layer with magnesium sulfate, concentrating and drying under reduced pressure to obtain solidAnd (4) transforming. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 5/1) to give the desired product (4.17g) as a pale yellow powder.¹H-NMR(CDCl₃): 2.17(3H, s), 5.39(2H, s), 7.54(1H, d, J ═ 8Hz), 7.58(1H, d, J ═ 8Hz), 7.69(1H, s), 7.79(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz), preparation 106-45-bromo-3- (2-chloro-4-cyanobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

Iron powder (2.29g) was added to a mixed solution of 6-bromo-2- (N- (2-chloro-4-cyanophenylmethyl) acetylamino) -3-nitropyridine (21.8g) in ethanol (33ml) -acetic acid (8.3ml) at room temperature, and the mixture was refluxed for 2 hours. The reaction solution was allowed to cool, and then insoluble matter was removed by filtration. The solvent was distilled off, and methylene chloride was added to the residue to extract the product. The solvent was distilled off, and the objective product (1.90g) was obtained as a pale yellow powder by silica gel column chromatography (dichloromethane/methanol ═ 30/1). ¹H-NMR(CDCl₃)：2.49(3H，s)，5.58(2H，s)，6.67(1H，d，J＝8Hz)，7.41(1H，d，J＝8Hz)，7.44(1H，d，J＝8Hz)，7.75(1H，s)，7.87(1H，d，J＝8Hz).Mass(ESI)：m/e 361，363(M+H)⁺Preparation example 106-53- (2-chloro-4-cyanophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

The same procedures used in preparation 26-2 were repeated except for using 5-bromo-3- (2-chloro-4-cyanophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (546mg) to give the desired product (482mg) as a white powder.¹H-NMR(CDCl₃)：2.54(3H，s)，3.98(3H，s)，5.70(2H，s)，6.73(1H，d，J＝8Hz)，7.42(1H，d，J＝8Hz)，7.76(1H，s)，8.09(1H，d，J＝8Hz)，8，16(1H，d，J＝8Hz).Mass(ESI)：m/e 341(M+H)⁺Preparation example 106-63- (2-chloro-4-cyanophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, from methyl 3- (2-chloro-4-cyanophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (67mg), the desired product (39mg) was obtained as a pale brown powder.¹H-NMR(DMSO-d₆)：2.52(3H，s)，5.68(2H，s)，6.72(1H，d，J＝8Hz)，7.69(1H，d，J＝8Hz)，8.01(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz)，8.20(1H，s).Mass(ESI)：m/e 325(M-H)^-Preparation example 107-12-chloro-4-phenyltoluene

The same procedures used in preparation example 11-2 were repeated except for using 2-chloro-4-iodotoluene (2.3g) to give the desired product (1.9g) as a pale brown oil.¹H-NMR(CDCl₃): 2.40(3H, s), 7.23-7.60(8H, m.) preparation 107-22-chloro-4-phenylbenzyl bromide

The same procedures used in preparation 93-1 were repeated except for using 2-chloro-4-phenyltoluene (3.6g) to give the desired product (3.22g) as colorless crystals.¹H-NMR(CDCl₃): 4.64(2H, s), 7.35-7.63(8H, m). mp 73-74 deg.C preparation of 107-36-bromo-2- (N- (2-chloro-4-phenylphenylmethyl) acetamido) -3-nitropyridine

According to the same manner as in preparation example 106-3, from 2- (acetylamino) -6-bromo-3-nitropyridine (1.0g) and brominated 2-chloro-4-phenylphenylmethyl group (1.1g), an amorphous aimed product (1.6g) was obtained. ¹H-NMR(CDCl₃): 2.25(3H, brs), 5.42(2H, brs), 7.32-7.70(9H, m), 8.11(1H, d, J ═ 8Hz). M/z 458(M-H) preparation 107-45-bromo-3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

According to the same manner as in preparation example 106-4, from 6-bromo-2- (N- (2-chloro-4-phenylphenylmethyl) acetylamino) -3-nitropyridine (3.56g), the objective product (2.80g) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 2.61(3H, s), 5.62(2H, s), 6.71(1H, d, J ═ 8Hz), 7.32-7.55(7H, m), 7.68(1H, s), 7.92(1H, d, J ═ 8Hz) mass (esi): m/z 414(M +1) preparation 108-16-bromo-2- (N- (2-chloro-4- (trifluoromethyl) benzyl) acetamido) -3-nitropyridine

The desired product (2.60g) was obtained from 2- (acetylamino) -6-bromo-3-nitropyridine (2.00g) and 2-chloro-1- ((methanesulfonyloxy) methyl) -4- (trifluoromethyl) benzene (2.33g) according to the same method as in preparation 106-3.¹H-NMR(CDCl₃)：2.20(3H，brs)，5.40(2H，brs)，7.53(2H，d，J＝8Hz)，7.66(1H，brs)，7.78(1H，d，J＝8Hz)，8Preparation 108-25-bromo-3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1H, d, J ═ 8Hz)

According to the same manner as in preparation example 106-4, from 6-bromo-2- (N- (2-chloro-4- (trifluoromethyl) benzyl) acetylamino) -3-nitropyridine (2.60g), the objective product (1.55g) was obtained as pale yellow crystals. ¹H-NMR(CDCl₃): 2.51(3H, s), 5.59(2H, s), 6.68(1H, d, J ═ 8Hz), 7.39(1H, brd, J ═ 8Hz), 7.41(1H, d, J ═ 8Hz), 7.73(1H, brs), 7.88(1H, d, J ═ 8Hz) masss (esi): m/z 406(M +1) mp 106-

According to the same method as in preparation example 26-2, 5-bromo-3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1.50g) gave the desired product (1.47g) as pale brown crystals.¹H-NMR(CDCl₃): preparation of 109-12-amino-6-bromo-3-nitropyridine hydrobromide in example 109.54 (3H, s), 3.99(3H, s), 5.71(2H, s), 6.73(1H, d, J ═ 8Hz), 7.38(1H, d, J ═ 8Hz), 7.72(1H, s), 8.08(1H, d, J ═ 8Hz), 8.17(1H, d, J ═ 8Hz)

2-amino-6-chloro-3-nitropyridine (20.2g) was suspended in a 30% hydrogen bromide/acetic acid solution (100ml), and the mixture was stirred at 90 ℃. After 4 hours, 30% hydrogen bromide/acetic acid solution (100ml) was added thereto, and the mixture was stirred at 90 ℃ for 1 hour. Hydrogen bromide gas was then added little by little to the reaction mixture while stirring was continued at 100 ℃ for 8 hours. The reaction mixture was allowed to cool, and the precipitate was collected by filtration, washed with hexane, and the objective product (33.0g) was pale yellow powder. ¹H-NMR(DMSO-d₆): 7.63(1H, d, J ═ 8Hz), 8.01(1H, d, J ═ 8Hz), preparation 109-22- (acetylamino) -6-bromo-3-nitropyridine

According to the same manner as in preparation example 106-2, from 2-amino-6-bromo-3-nitropyridine hydrobromide (50.0g) and acetic anhydride (100ml), the objective product (40.7g) was obtained as a pale yellow powder.¹H-NMR(CDCl₃)：2.54(3H，s)，7.34(1H，d，J＝8Hz)，8.34(1H，d，J＝8Hz)，9.98(1H，brs).Mass(ESI)：m/e 260(M-1)^-Preparation example 109-35-bromo-2-methyl-1H-imidazo [ 4, 5-b ] pyridine

The desired product (2.48g) was obtained as pale yellow crystals from 2- (acetylamino) -6-bromo-3-nitropyridine (4.0g) by the same method as in production example 106-4.¹H-NMR(DMSO-d₆): 2.51(3H, s), 7.32(1H, d, J ═ 8Hz), 7.83(1H, d, J ═ 8Hz). M/z 210(M-1) mp 239-

Palladium acetate (1.18g), 1, 3-bis (diphenylphosphino) propane (2.31g), and 5-bromo-2-methyl-1H-imidazo [ 4, 5-b ] pyridine (3.72g) were charged into an autoclave, and N, N-dimethylformamide (18.6ml), methanol (14.9ml), and triethylamine (5.4ml) were added thereto, and the mixture was stirred at 85 ℃ for 14 hours in a carbon monoxide atmosphere of 10 atm. The reaction mixture was cooled, the solvent was distilled off, and methanol (60ml) was added to the residue, which was then heated, and the insoluble matter was removed by filtration while it was hot. The filtrate was concentrated to give the desired product (2.95g) as a white powder. ¹H-NMR(CDCl₃)：2.82(3H，s)，4.05(3H，s)，8.04(1H，d，J＝8Hz)，8.10(1H，d，J＝8Hz).Mass(ESI)：m/e 192(M+1)⁺Preparation example 110-16-bromo-2- (N- (2, 4-dichlorobenzyl) acetylamino) -3-nitropyridine

The same procedures used in preparation 106-3 were repeated except for using 2- (acetylamino) -6-bromo-3-nitropyridine (10.0g) and 2, 4-dichlorobenzyl chloride (8.3g) to give the desired product (11.71g) as a pale yellow powder.¹H-NMR(CDCl₃): preparation of 110-25-bromo-3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (3H, brs), 5.33(2H, brs), 7.24(2H, d, J ═ 8Hz), 7.30-7.68(3H, m), 8.11(1H, d, J ═ 8Hz)

The same procedures used in preparation 106-4 were repeated except for using 6-bromo-2- (N- (2, 4-dichlorobenzyl) acetylamino) -3-nitropyridine (11.7g) to give the desired product (4.27g) as a pale yellow powder.¹H-NMR(CDCl₃)：2.48(3H，s)，5.50(2H，s)，6.54(1H，d，J＝8Hz)，7.12(1H，dd，J＝8 and 2Hz)，7.39(1H，d，J＝8Hz)，7.47(1H，d，J＝2Hz)，7.86(1H，d，J＝8Hz).Mass(ESI)：m/e 370，372(M+H)⁺Preparation example 111-13-chloro-4-methylbenzyl alcohol

The same procedures used in preparation example 74-4 were repeated except for using 3-chloro-4-methylbenzoic acid (25.0g) to give the desired product (23.0g) as a colorless oil.¹H-NMR(CDCl₃): preparation of 111-23-chloro-4-methylbenzaldehyde from 2.36(3H, S), 4.65(2H, S), 7.14(1H, d, J ═ 8Hz), 7.23(1H, d, J ═ 8Hz), 7.36(1H, S)

To a solution of 3-chloro-4-methylbenzyl alcohol (2.00g) and triethylamine (8.9ml) in dimethyl sulfoxide (10ml) was added sulfur trioxide-pyridine complex (4.47g) under ice bath conditions, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ether. The extract was washed with 1N hydrochloric acid, saturated brine and saturated aqueous solution of sodium hydrogencarbonate, dried over magnesium sulfate, and then concentrated and dried under reduced pressure to solidify the extract, whereby the desired product (1.40g) was obtained as a pale yellow oil. ¹H-NMR(CDCl₃): preparation of 111-32-chloro-4- (E) - (2-phenylvinyl) toluene was 2.46(3H, s), 4.65(2H, s), 7.40(1H, d, J ═ 8Hz), 7.68(1H, d, J ═ 8Hz), 9.92(1H, s)

According to the same method as in preparation example 73-3, from 3-chloro-4-methylbenzaldehyde (1.40g) and diethyl benzylphosphate (2.27g), the objective product (1.55g) was obtained as a white powder.¹H-NMR(CDCl₃): 2.38(3H, s), 7.00(1H, d, J ═ 16Hz), 7.08(1H, d, J ═ 16Hz), 7.18 to 7.53(8H)

The desired product (309mg) was obtained as a white powder from 2-chloro-4- (E) - (2-phenylvinyl) toluene (1.35g) in the same manner as in preparation example 93-1.¹H-NMR(CDCl₃): 4.61(2H, s), 7.01(1H, d, J ═ 16Hz), 7.14(1H, d, J ═ 16Hz), 7.24 to 7.57(8H) preparation 112-13- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5 carboxylic acid methyl ester

3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) Methyl (2.37g) of (e) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate was dissolved in 1/4(24ml) methanol/chloroform, and platinum (IV) oxide (169mg) was added thereto. After stirring for 4 hours under an atmospheric hydrogen atmosphere, platinum (IV) oxide (169mg) was further added, and further stirring was carried out for 6 hours under an atmospheric hydrogen atmosphere. The reaction mixture was filtered through celite, the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography and eluted with ethyl acetate/chloroform-1/3. The fractions of the desired product were concentrated under reduced pressure to give the desired product (1.92g) as a white powder. ¹H-NMR(CDCl₃): 2.53(3H, s), 2.88(4H, s), 4.01(3H, s), 5.64(2H, s), 6.53(1H, d, J ═ 8Hz), 6.89(1H, dd, J ═ 2.8Hz), 7.12 to 7.30(6H, m), 8.04(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz), preparation 112-23- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.89g) was used to give the desired product (1.79g) as white crystals.¹H-NMR(DMSO-d₆): 2.50(4H, s), 2.84(3H, s), 5.57(2H, s), 6.45(1H, d, J ═ 8Hz), 7.09(1H, dd, J ═ 2.8Hz), 7.15 to 7.20(5H, m), 7.43(1H, s), 7.99(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), preparation 113-13-chloro-4-methylbenzoic acid ethyl ester

The same procedures used in preparation example 74-2 were repeated except for using 3-chloro-4-methylbenzoic acid (28.7g) to give the desired product (28.7g) as a pale yellow oil.¹H-NMR(CDCl₃): 1.39(3H, t, J ═ 6Hz), 2.43(3H, s), 4.38(2H, q, J ═ 6Hz), 7.29(1H, d, J ═ 8Hz), 7.83(1H, d, J ═ 8Hz), 8.02(1H, s) preparation 113-24-bromomethyl-3-chlorobenzoic acid ethyl ester

The same procedures used in preparation 93-1 were repeated except for using ethyl 3-chloro-4-methylbenzoate (28.7g) to give the desired product (39.9g) as a pale yellow oil. ¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 6Hz), 4.39(2H, q, J ═ 6Hz), 4.60(2H, s), 7.52(1H, d, J ═ 8Hz), 7.92(1H, d, J ═ 8Hz), 8.06(1H, s) preparation 113-36-bromo-2-(N- (4-ethoxycarbonyl-2-chlorophenylmethyl) acetamido) -3-nitropyridine

The desired product (40.91g) was obtained from 2-acetylamino-6-bromo-3-nitropyridine (24.7g) and ethyl 4-bromomethyl-3-chlorobenzoate (44.8g) according to the same method as in preparation 106-3.¹H-NMR(CDCl₃): preparation of 113-45-bromo-3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1.40 (3H, t, J ═ 6Hz), 2.20(3H, s), 4.40(2H, q, J ═ 6Hz), 5.40(2H, s), 7.16-8.22(5H)

According to the same manner as in preparation example 106-4, from 2- [ N-acetyl-N- (2-chloro-4- (ethoxycarbonyl) benzyl) ] amino-6-bromo-3-nitropyridine (40.8g), the desired product (32.0g) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 1.38(3H, t, J ═ 7.5Hz), 4.36(2H, q, J ═ 7.5Hz), 5.57(2H, s), 6.61(1H, d, J ═ 8Hz), 7.40(1H, d, J ═ 8Hz), 7.77(1H, d, J ═ 8Hz), 7.88(1H, d, J ═ 8Hz), 8.11(1H, s) preparation 113-53- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

5-bromo-3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (4.92g) was dissolved in a mixed solvent of N, N-dimethylformamide (27.6ml) and tert-butanol (21.7ml) in a sealed test tube, and triethylamine (2.84g), 1, 3-bis (diphenylphosphino) propane (1.59g) and palladium (II) acetate (865mg) were added. The test tube was sealed and stirred at 85 ℃ for 24 hours in a carbon monoxide atmosphere of 10 atm. Triethylamine (1.42g), 1, 3-bis (diphenylphosphino) propane (795mg), and palladium (II) acetate (433mg) were sequentially added thereto, and the test tube was sealed again and stirred under heating at 85 ℃ for 12 hours in a carbon monoxide atmosphere of 10 atmospheres. The reaction solution was filtered, and the residue was washed with chloroform, and then the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, eluted with methanol/chloroform (1/49), and the fractions of the desired product were concentrated under reduced pressure. To the residue was added ethyl acetate (50ml), which was heated in a hot water bath and allowed to cool while stirring at room temperature. The precipitated crystals were collected by filtration to obtain the objective product (3.61g) as pale yellow crystals.¹H-NMR(DMSO-d₆): preparation 114-15-bromo-3- (2-chloro-4- (hydroxymethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine [ 7H, 7Hz ], 2.50(3H, s), 4.28(2H, q, J ═ 7Hz), 5.08(2H, s), 6.70(1H, d, J ═ 8Hz), 7.76(1H, d, J ═ 8Hz), 8.00-8.03(2H, m), 8.14(1H, d, J ═ 8Hz)

The same procedures used in preparation example 76-2 were repeated except for using 5-bromo-3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (15.0g), to give the desired product (11.5g) as pale yellow crystals.¹H-NMR(DMSO-d₆): 2.46(3H, s), 4.47(2H, d, J ═ 5Hz), 5.32(1H, t, J ═ 5Hz), 5.50(2H, s), 6.55(1H, d, J ═ 8Hz), 7.16(1H, d, J ═ 8Hz), 7.44(1H, d, J ═ 8Hz), 7.48(1H, s), 7.99(1H, d, J ═ 8Hz) ms esi (m/e): 366.368. preparation example 114-23- (2-chloro-4- (hydroxymethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine 5-carboxylic acid methyl ester

The same procedures used in preparation 26-2 were repeated except for using 5-bromo-3- (2-chloro-4- (hydroxymethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (12.7g) to give the desired product (9.95g) as pale yellow crystals.¹H-NMR(DMSO-d₆): 2.50(3H, s), 3.86(3H, s), 4.46(2H, d, J ═ 5Hz), 5.31(1H, t, J ═ 3Hz), 5.59(2H, s), 6.53(1H, d, J ═ 8Hz), 7.14(1H, d, J ═ 8Hz), 7.49(1H, s), 8.02(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms (esi) m/e: 346(M + H), 691(2M + H), 713(2M + Na). preparation 114-33- (2-chloro-4- ((methanesulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in preparation example 14-1, from methyl 3- (2-chloro-4- (hydroxymethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (3.6g) and methanesulfonyl chloride (1.43g), the objective product (4.2g) was obtained as pale yellow crystals.¹H-NMR(CDCl₃)：2.54(3H，s)，3.00(3H，s)，4.00(3H，s)，5.16(2H，s)，5.68(2H，s)，6.65(1H，d，J＝8Hz)，7.15(1H，d，J＝8Hz)，7.51(1H，s)，8.07(1H，d，J＝8Hz)，8.15(1H，d，J＝8Hz)MS(ESI)m/e：424(M+H)，446(M+Na)，Preparation 114-43- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in example 118 described below, from methyl 3- (2-chloro-4- ((methanesulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.8g), the objective product (1.94g) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 2.54(3H, s), 4.00(3H, s), 5.01(2H, s), 5.69(2H, s), 6.63(1H, d, J ═ 8Hz), 6.91-7.01(3H, m), 7.16(1H, d, J ═ 8Hz), 7.25-7.34(2H, m), 7.55(1H, s), 8.07(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms (esi) m/e: 422(M + H). preparation 114-53- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.94g) was used to obtain the desired product (1.54g) as pale yellow crystals. ¹H-NMR(DMSO-d₆): 2.50(3H, s), 5.08(2H, s), 5.64(2H, s), 6.52(1H, br peak), 6.89-7.03(3H, m), 7.23-7.34(3H, m), 7.64(1H, s), 7.98(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz) ms (esi) m/e: 406(M-H) preparation 115-13- (2-chloro-4- (dimethylaminomethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in the following preparation example 116-1, from methyl 3- (2-chloro-4- ((methanesulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) and dimethylamino hydrochloride (115mg), the desired product (128mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 2.25(6H, s), 2.52(3H, s), 3.40(2H, s), 3.99(3H, s), 5.67(2H, s), 6.58(1H, d, J ═ 8Hz), 7.06(1H, d, J ═ 8Hz), 7.45(1H, s), 8.07(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms (esi) m/e: 373(M + H). preparation of 115-23- (2-chloro-4- (dimethylaminomethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same procedures as in preparation examples 4 to 7Process, from methyl 3- (2-chloro-4- (dimethylaminomethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (120mg), the desired product was obtained as pale yellow crystals (116 mg). ¹H-NMR(DMSO-d₆): 2.45-2.61(9H, m), 4.04(2H, br peak), 5.63(2H, s), 6.62(1H, d, J ═ 8Hz), 7.33(1H, d, J ═ 8Hz), 7.74(1H, s), 8.01(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms (esi) m/e: 357(M-H). preparation 116-13- (2-chloro-4- ((imidazol-1-yl) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

To a solution of methyl 3- (2-chloro-4- ((methylsulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (300mg) in dichloromethane (6.0ml) was added imidazole (193mg), and the mixture was stirred at room temperature overnight. The reaction solution was poured into water, and extracted with chloroform. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated and dried under reduced pressure to solidify the organic layer. The residue was washed with diethyl ether and filtered to give the desired product (213mg) as a pale yellow powder.¹H-NMR(CDCl₃): 2.53(3H, s), 3.99(3H, s), 5.08(2H, s), 5.65(2H, s), 6.62(1H, d, J ═ 8Hz), 6.84-6.93(2H, m), 7.11(1H, s), 7.21(1H, s), 7.53(1H, s), 8.06(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms (esi) m/e: 396(M + H). preparation 116-23- (2-chloro-4- ((imidazol-1-yl) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- ((imidazol-1-yl) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (235mg) was used to obtain the objective product (204mg) as pale yellow crystals.¹H-NMR(DMSO-d₆): 2.50(3H, s), 5.21(2H, s), 5.58(2H, s), 6.65(1H, d, J ═ 8Hz), 7.00(1H, s), 7.10(1H, d, J ═ 8Hz), 7.26(1H, s), 7.47(1H, s), 7.93(1H, s), 7.99(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) ms (esi) m/e: 380.1(M-H). preparation 117-13- (2-chloro-4- ((piperidin-1-yl) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same phase as that of preparation 116-1In the same manner, methyl 3- (2-chloro-4- ((methylsulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) and piperidine (80mg) were used to give the desired product (174mg) as pale yellow crystals.¹H-NMR(CDCl₃): 1.36-1.48(2H, m), 1.48-1.64(4H, m), 2.27-2.40(4H, m), 2.54(3H, s), 3.40(2H, s), 4.00(3H, s), 5.66(2H, s), 6.54(1H, d, J ═ 8Hz), 7.04(1H, d, J ═ 8Hz), 7.43(1H, s), 8.06(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms (esi) m/e: 413.2(M + H). preparation 117-23- (2-chloro-4- ((piperidin-1-yl) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- ((piperidin-1-yl) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (169mg) was used to give the objective product (153mg) as pale yellow crystals.¹H-NMR(DMSO-d₆): 1.45(2H, br peak), 1.64(4H, br peak), 2.54(3H, s), 2.79(4H, br peak), 4.02(2H, br peak), 5.62(2H, s), 6.60(1H, d, J ═ 8Hz), 7.31(1H, d, J ═ 8Hz), 7.73(1H, s), 8.00(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms (esi) m/e: 399.3(M + H.) preparation 118-13- (2-chloro-4- (phenylthiomethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in example 118 described below, from methyl 3- (2-chloro-4- ((methanesulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) and thiophenol (62mg), the objective product (182mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 2.50(3H, s), 4.00(3H, s), 4.01(2H, s), 5.63(2H, s), 6.51(1H, d, J ═ 8Hz), 6.98(1H, d, J ═ 8Hz), 7.15-7.30(5H, m), 7.36(1H, s), 8.04(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz) ms esi) m/e: 438. preparation example 118-23- (2-chloro-4- (phenylthiomethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

From methyl 3- (2-chloro-4- (phenylthiomethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (217mg) the desired product was obtained as pale yellow crystals(191mg)。¹H-NMR(DMSO-d₆): 2.47(3H, s), 4.21(2H, s), 5.58(2H, s), 6.50(1H, d, J ═ 8Hz), 7.11-7.22(2H, m), 7.22-7.34(4H, m), 7.53(1H, s), 8.00(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) ms (esi) m/e: 422(M-H). preparation example 119-13- (4- ((benzyloxy) methyl) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

To a suspension of methyl 3- (2-chloro-4- (hydroxymethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (400mg) in dimethylformamide (8.0ml) were added sodium hydride (51mg) and benzyl bromide (277mg) under ice-bath conditions, and the mixture was stirred at the same temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, and chloroform and sodium hydrogencarbonate were added to the residue to separate the mixture. The organic layer was washed with saturated brine, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluting with chloroform-methanol at 50: 1) to give the desired product (322mg) as a pale yellow powder.¹H-NMR(CDCl₃): 2.53(3H, s), 3.99(3H, s), 4.48(2H, s), 4.55(2H, s), 5.66(2H, s), 6.59(1H, d, J ═ 8Hz), 7.08(1H, d, J ═ 8Hz), 7.26 to 7.41(5H, m), 7.46(1H, s), 8.06(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms esi (m/e): 436. preparation example 119-23- (4- ((benzyloxy) methyl) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4- ((benzyloxy) methyl) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (352mg) was used to give the desired product (232mg) as pale yellow crystals.¹H-NMR(DMSO-d₆): 4.51(4H, s-like), 5.62(2H, s), 6.55(1H, d, J ═ 8Hz), 7.21(1H, d, J ═ 8Hz), 7.24-7.40(5H, m), 7.53(1H, s), 8.01(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz) ms (esi) m/e: 420(M-H). preparation of 120-15-bromo-3- (4-carboxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

According to the same manner as in preparation examples 4 to 7, from 5-bromo-3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (6.0)g) The desired product was obtained as pale yellow crystals (5.3 g).¹H-NMR(DMSO-d₆): 2.50(3H, s), 5.57(2H, s), 6.70(1H, d, J ═ 8Hz), 7.45(1H, d, J ═ 8Hz), 7.79(1H, d, J ═ 8Hz), 7.95-8.09(2H, m) ms (esi) m/e: 378, 380, 382. preparation example 120-25-bromo-3- (4- (benzimidazol-2-yl) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

To a solution of 5-bromo-3- (4-carboxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (2.75g) in N, N-dimethylformamide (30m1) were added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.66g), 1-hydroxybenzotriazole (1.37g) and 1, 2-phenylenediamine (781mg) at room temperature, and the mixture was stirred for 1 hour. The reaction mixture was left under the same conditions overnight, concentrated and dried under reduced pressure to solidify, and the residue was separated from chloroform and a saturated aqueous solution of sodium hydrogencarbonate. After a part of the precipitated solid was collected by filtration, the organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The solid obtained by the previous filtration was combined with the residue, which was washed with diethyl ether to give the amide-based compound (2.97 g).

To a suspension of the obtained amide-based compound (2.97g) in ethanol (100ml) was added p-toluenesulfonic acid monohydrate (150mg), and the mixture was refluxed for 48 hours, and then the residue was separated from chloroform and a saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with chloroform-methanol mixture (10: 1), and the organic layers were combined, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was washed with ethyl acetate and filtered to give the desired product (2.39g) as a pale yellow powder.¹H-NMR(DMSO-d₆): 2.52(3H, s), 5.59(2H, s), 6.81(1H, d, J ═ 8Hz), 7.17-7.26(2H, m), 7.47(1H, d, J ═ 8Hz), 7.55-7.65(2H, m), 7.97-8.06(2H, m), 8.33(1H, s) ms (esi) m/e: 450, 452, 454 preparation example 120-33- [ 4- (benzimidazol-2-yl) -2-chlorophenylmethyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation 26-2, from 5-bromo-3- (4- (benzimidazol-2-yl) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1.85g), the desired product (1.38g) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆): 2.58(3H, s), 3.86(3H, s), 5.68(2H, s), 6.80(1H, d, J ═ 8Hz), 7.17-7.27(2H, m), 7.55-7.66(2H, m), 7.98-8.09(2H, m), 8.19(1H, d, J ═ 8Hz), 8.35(1H, s) ms (esi) m/e: 430 (M-H.) preparation 120-43- (4- (benzimidazol-2-yl) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4- (benzimidazol-2-yl) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (300mg) gave the desired product (260mg) as pale yellow crystals.¹H-NMR(DMSO-d₆): 2.58(3H, s), 5.70(2H, s), 6.81(1H, d, J ═ 8Hz), 7.21-7.31(2H, m), 7.60-7.69(2H, m), 7.98-8.06(2H, m), 8.16(1H, d, J ═ 8Hz), 8.37(1H, s) ms (esi) m/e: 416(M-H) preparation 121-12-methyl-3- [ 4- (1-methylbenzimidazol-2-yl) -2-chlorophenylmethyl ] -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

A mixture of methyl 3- [ 4- (benzimidazol-2-yl) -2-chlorophenylmethyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (325mg), methyl iodide (107mg), potassium carbonate (198mg) and dimethylformamide (10ml) was stirred overnight at room temperature, and then concentrated and dried under reduced pressure to solidify. The residue was suspended in chloroform, and washed with a saturated aqueous sodium bicarbonate solution and a saturated brine 1 time. The organic layer was dried over magnesium sulfate, concentrated and dried under reduced pressure to solidify, and the residue was pulverized in diethyl ether to obtain the desired product (282mg) as a pale yellow powder.¹H-NMR(CDCl₃): 2.60(3H, s), 3.85(3H, s), 4.01(3H, s), 5.78(2H, s), 6.77(1H, d, J ═ 8Hz), 7.27-7.44(3H, m), 7.50(1H, d, J ═ 8Hz), 7.76-7.84(1H, m), 7.95(1H, s), 8.10(1H, d, J ═ 8Hz), 8.17(1H, d, J ═ 8Hz) ms (esi) m/e: 446(M + H) preparation 121-22-methyl-3- [ 4- (1-methylbenzimidazol-2-yl) -2-chlorobenzyl ] -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

By the same method as in preparation examples 4 to 7 from 2-methyl-3- [ 4- (1-methylbenzimidazol-2-yl) -2-chlorophenylmethyl ] -3H-imidazo [ 4, 5-bPyridine-5-carboxylic acid methyl ester (268mg) gave the objective product (215mg) as pale yellow crystals.¹H-NMR(DMSO-d₆): 2.59(3H, s), 3.88(3H, s), 5.74(2H, s), 6.72(1H, d, J ═ 8Hz), 7.20-7.40(2H, m), 7.59-7.80(3H, m), 7.98-8.13(2H, m), 8.18(1H, d, J ═ 8Hz) ms (esi) m/e: 430(M-H). preparation examples 122-13- ((benzimidazol-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- ((benzimidazol-2-yl) methyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, from methyl 2-methylimidazo [ 4, 5-b ] pyridine-5-carboxylate (100mg), methyl 3- ((benzimidazol-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (20mg) and methyl 1- ((benzimidazol-2-yl) methyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (20mg) were obtained as brown powders.

3- ((benzimidazol-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃)：2.88(3H，s)，4.10(3H，s)，5.69(2H，s)，7.20-7.80(4H)，8.03(1H，d，J＝8Hz)，8.12(1H，d，J＝8Hz)

1- ((benzimidazol-2-yl) methyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester ¹H-NMR(CDCl₃): preparation of 122-23- ((1-ethylbenzimidazol-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester 2.30(3H, s), 3.83(3H, s), 5.66(2H.s), 7.18-7.88(6H)

According to the same manner as in preparation example 121-1, methyl 3- ((benzimidazol-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (380mg) and methyl iodide (194mg) were used to obtain the desired product (192mg) as yellow crystals.¹H-NMR(CDCl₃): 1.08(3H, t, J ═ 7.5Hz), 2.85(3H, s), 4.04(3H, s), 4.51(2H, q, J ═ 7.5Hz), 5.83(2H, s), 7.23-7.38(3H, m), 7.71-7.80(1H, m), 8.02(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz) ms esi) m/e: 350(M + H). preparation 122-33- ((1-ethylbenzimidazol-2-yl) methyl) -2-methyl-3H-imidazoleAnd [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- ((1-ethylbenzimidazol-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (226mg) gave the desired product (110mg) as pale yellow crystals.¹H-NMR(DMSO-d₆): 1.33(3H, t, J ═ 7.5Hz), 2.68(3H, s), 4.53(2H, q, J ═ 7.5Hz), 5.91(2H, s), 7.14(1H, t, J ═ 8Hz), 7.24(1H, t, J ═ 8Hz), 7.50(1H, d, J ═ 8Hz), 7.60(1H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz) ms (esi) m/e: 334(M-H). preparation 123-12-chloro-4- (thien-2-yl) toluene

The same procedures as in preparation example 11-2 were repeated except for using 2-chloro-4-iodotoluene (7.89g) and thiophene 2-boronic acid (4.8g) to give the desired product (6.50 g).¹H-NMR(CDCl₃): 2.38(3H, s), 7.07(1H, dd, J ═ 5.4Hz), 7.22(1H, d, J ═ 8Hz), 7.24-7.30(2H), 7.39(1H, d, J ═ 8Hz), 7.60(1H, s) preparation 123-22-chloro-4- (thiophen-2-yl) benzyl bromide

The desired product (1.35g) was obtained from 2-chloro-4- (thiophen-2-yl) toluene (1.00g) according to the same method as in preparation 93-1.¹H-NMR(CDCl₃): 4.61(2H, s), 7.09(1H, t, J ═ 4Hz), 7.30-7.52(4H), 7.63(1H, s) preparation 123-36-bromo-2- (N- (2-chloro-4- (thiophen-2-yl) benzyl) acetamido) -3-nitropyridine

The desired product (1.60g) was obtained from 2-acetylamino-6-bromo-3-nitropyridine (1.24g) and 2-chloro-4- (thiophen-2-yl) benzyl bromide (1.35g) according to the same method as in preparation 106-3.¹H-NMR(CDCl₃): 2.24(3H, br.s), 5.39(2H, br.s), 7.09(1H, t, J ═ 4Hz), 7.29-7.34(2H), 7.50(1H, br.d, J ═ 8Hz), 7.62(1H, br.d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz) preparation 123-45-bromo-3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

The desired product (647mg) was obtained from 6-bromo-2- (N- (2-chloro-4- (thiophen-2-yl) benzyl) acetylamino) -3-nitropyridine (836mg) according to the same process as in preparation 106-4. ¹H-NMR(CDCl₃): preparation of 123-53- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (3H, br.s), 5.56(2H, s), 6.60(1H, d, J ═ 8Hz), 7.08(1H, t, J ═ 5Hz), 7.26-7.42(4H), 7.67(1H, s), 7.87(1H, d, J ═ 8Hz)

According to the same manner as in preparation 26-2, from 5-bromo-3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (4.7g), the desired product (4.0g) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 2.56(3H, s), 4.00(3H, s), 5.69(3H, s), 6.64(1H, d, J ═ 8Hz), 7.07(1H, dd, J ═ 5.4Hz), 7.22-7.37(3H, m), 7.67(1H, d, J ═ 2Hz), 8.07(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz) ms esi (m/e): 398.0(M + H) preparation 124-13- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine 5-carboxylic acid methyl ester

According to the same method as in preparation example 102-5, methyl 2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (900mg) was used to obtain the desired product (1.48g) as colorless crystals. mp 202-¹H-NMR(CDCl₃): 2.58(3H, s), 2.75(3H, s), 3.99(3H, s), 5.70(2H, s), 6.65(1H, d, J ═ 8Hz), 7.23-7.45(4H, m), 7.51(2H, d, J ═ 8Hz), 7.66(1H, s), 7.99(1H, s) ms (esi) m/z: 406(M +1) preparation 124-23- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in preparation example 14-2, methyl 2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.85g) gives the desired product (4.60g) as colorless crystals. mp 160-¹H-NMR(CDCl₃): 2.57(3H, s), 2.75(3H, s), 4.00(3H, s), 5.67(2H, s), 6.61(1H, d, J ═ 8Hz), 7.07(1H, t, J ═ 4Hz), 7.25-7.35(3H, m), 7.67(1H, d, J ═ 1Hz), 7.99(1H, d, J ═ 8Hz), 8.16(1H, d, J ═ 8Hz) ms (esi) m/z: 412(M +1) preparation 125-13- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According toThe same procedures used in preparation examples 4 to 7 were repeated except for using methyl 3- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.45g) to give the desired product (1.33g) as colorless crystals. mp > 250 deg.C¹H-NMR(DMSO-d₆): 2.55(3H, s), 2.64(3H, s), 5.64(2H, s), 6.56(1H, d, J ═ 8Hz), 7.35-7.54(4H, m), 7.62-7.67(2H, m), 7.84-7.89(2H, m) ms (esi) m/z: 392(M +1) preparation 125-23- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.0g) was used to obtain the desired product (1.81g) as colorless crystals. mp > 250 deg.C ¹H-NMR(DMSO-d₆): 2.53(3H, s), 2.64(3H, s), 5.61(2H, s), 6.55(1H, d, J ═ 8Hz), 7.14(1H, t, J ═ 4Hz), 7.49(1H, dd, J ═ 8.1Hz), 7.58(1H, s), 7.60(1H, brs), 7.87(2H, s) ms (esi) m/z: 396(M-1). preparation 126-13- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in preparation 66-1, from methyl 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.55g), the desired product (1.72g) was obtained as colorless crystals.¹H-NMR(CDCl₃): 2.55(3H, s), 2.74(3H, s), 3.98(3H, s), 5.60(2H, s), 6.60(1H, d, J ═ 8Hz), 6.88(1H, d, J ═ 4Hz), 7.04(1H, d, J ═ 4Hz), 7.21(1H, dd, J ═ 8.1Hz), 7.57(1H, d, J ═ 1Hz), 7.98(1H, s) ms (esi) m/z: 446(M +1). preparation 126-23- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.23g) was used to obtain the desired product (1.08g) as colorless crystals. mp > 250 deg.C ¹H-NMR(DMSO-d₆)：2.53(3H，s)，2.63(3H，s)，5.60(2H，s)，6.54(1H，d，J＝8Hz), 7.17(1H, d, J ═ 4Hz), 7.42(1H, dd, J ═ 8.1Hz), 7.49(1H, d, J ═ 4Hz), 7.84-7.88(2H, m) ms (esi) m/z: 430(M-1) preparation example 127-12-chloro-4- (n-pentylthio) benzoic acid methyl ester

The desired product (438mg) was obtained as a colorless oil from methyl 4-bromo-2-chlorobenzoate (1g) in the same manner as in preparation example 80-1.¹H-NMR(CDCl₃): 0.90(3H, t, J ═ 8Hz), 1.29-1.51(4H, m), 1.64-1.76(2H, m), 2.96(2H, t, J ═ 8Hz), 3.90(3H, s), 7.14(1H, dd, J ═ 8.1Hz), 7.29(1H, d, J ═ 1Hz), 7.78(1H, d, J ═ 8Hz) preparation of methyl 127-24-benzylthio-2-chlorobenzoate

The desired product (908mg) was obtained as a colorless oil from methyl 4-bromo-2-chlorobenzoate (1g) in the same manner as in preparation example 80-1.¹H-NMR(CDCl₃): 3.91(3H, s), 4.19(2H, s), 7.15(1H, dd, J ═ 8.1Hz), 7.23 to 7.43(6H, m), 7.75(1H, d, J ═ 8Hz) preparation of methyl 127-32-chloro-4-ethylsulfanylbenzoate

According to the same manner as in preparation example 80-1, methyl 4-bromo-2-chlorobenzoate (3.65g) was used to give the objective product (2.01g) as a colorless oil.¹H-NMR(CDCl₃): 1.37(3H, t, J ═ 7.5Hz), 3.01(2H, q, J ═ 7.5Hz), 3.91(3H, s), 7.15(1H, dd, J ═ 8.1Hz), 7.29(1H, d, J ═ 1Hz), 7.78(1H, d, J ═ 8Hz), preparation 128-12-chloro-4- (n-pentylthio) benzyl alcohol

According to the same manner as in preparation example 80-2, methyl 2-chloro-4- (n-pentylthio) benzoate (430mg) was used to give the objective product (354mg) as a colorless oil.¹H-NMR(CDCl₃): 0.90(3H, t, J ═ 8Hz), 1.29-1.49(4H, m), 1.60-1.72(2H, m), 1.89(1H, t, J ═ 5Hz), 2.91(2H, t, J ═ 8Hz), 4.74(2H, d, J ═ 5Hz), 7.20(1H, d, J ═ 8Hz), 7.29(1H, brs), 7.38(1H, d, J ═ 8Hz), preparation 128-24-benzylthio-2-chlorobenzyl alcohol

According to the same method as in preparation example 80-2, methyl 4-benzylthio-2-chlorobenzoate (900mg) gave the objective product (787mg) as a colorless oil.¹H-NMR(CDCl₃): preparation of 128-32-chloro-4-ethylthiomethylmethanol from 1.88(1H, t, J ═ 7Hz), 4.11(3H, s), 4.73(2H, d, J ═ 7Hz), 4.19(2H, s), 7.19(1H, d, J ═ 8Hz), 7.21-7.32(6H, m), 7.36(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 80-2, methyl 2-chloro-4-ethylsulfanylbenzoate (2.0g) was used to give the desired product (1.69g) as a colorless oil.¹H-NMR(CDCl₃): example 129-12-chloro-1- ((methanesulfonyloxy) methyl) -4- (n-pentylthio) benzene, preparation of 1.32(3H, t, J ═ 7.5Hz), 1.92(1H, t, J ═ 7Hz), 2.95(2H, q, J ═ 7.5Hz), 4.74(2H, d, J ═ 7Hz), 7.21(1H, dd, J ═ 8.1Hz), 7.30(1H, d, J ═ 1Hz), 7.38(1H, d, J ═ 8Hz)

The desired product was obtained from 2-chloro-4- (n-pentylthio) benzyl alcohol (350mg) according to the same method as in preparation example 14-1. The reaction mixture was used in the following reaction without purification. Preparation example 129-24-Phenylmethylthio-1- ((methylsulfonyloxy) methyl) -2-chlorobenzene

The desired product was obtained from 4-benzylthio-2-chlorobenzyl alcohol (350mg) according to the same manner as in preparation example 14-1. The reaction mixture was used in the following reaction without purification. Preparation example 129-32-chloro-4-ethylthio-1- ((methanesulfonyloxy) methyl) benzene

The desired product was obtained from 2-chloro-4-ethylthiomethyl alcohol (1.66g) according to the same method as in preparation example 14-1. The reaction mixture was used in the following reaction without purification. Preparation examples 130-13- [ 2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- [ 2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (273mg) gave methyl 3- [ 2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (207mg) and amorphous methyl 1- [ 2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (293mg) as pale yellow crystals.

3-〔2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester mp 64-65 deg.C¹H-NMR(CDCl₃)：0.89(3H，t，J＝7.5Hz)，1.26-1.46(4H，m)，1.59-1.70(2H，m)，2.54(3H，s)，2.89(2H，t，J＝7.5Hz)，4.00(3H，s)，5.63(2H，s)，6.55(1H，d，J＝8Hz)，7.00(1H，d，J＝8Hz)，7.34(1H，d，J＝1Hz)，8.06(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz)MS(ESI)m/z：418(M+1).

1- [ 2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7.5Hz), 1.26-1.47(4H, m), 1.59-1.71(2H, m), 2.65(3H, s), 2.90(2H, t, J ═ 7.5Hz), 4.01(3H, s), 5.39(2H, s), 6.40(1H, d, J ═ 8Hz), 7.01(1H, dd, J ═ 8.1Hz), 7.35(1H, brs), 7.56(1H, d, J ═ 8Hz), 8.09(1H, d, J ═ 8Hz) ms (esi) m/z: 418(M +1) preparation of 130-23- [ 4- (benzylthio) -2-chloro ] benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester and 1- [ 4- (benzylthio) -2-chloro ] benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (554mg) gave methyl 3- [ 4- (benzylthio) -2-chloro ] benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (592mg) and amorphous methyl 1- [ 4- (benzylthio) -2-chloro ] benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (495mg) as pale yellow crystals.

Methyl 3- [ 4- (benzylthio) -2-chloro ] benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate mp 140-¹H-NMR(CDCl₃)：2.51(3H，s)，4.00(3H，s)，4.09(2H，s)，5.61(2H，s)，6.51(1H，d，J＝8Hz)，6.99(1H，d，J＝8Hz)，7.23-7.31(5H，m)，7.34(1H，brs)，8.05(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz)MS(ESI)m/z：438(M+1).

1- [ 4- (phenylmethylthio) -2-chloro ] benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyrazinePyridine-5-carboxylic acid methyl ester¹H-NMR(CDCl₃): 2.64(3H, s), 4.00(3H, s), 4.10(2H, s), 5.38(2H, s), 6.38(1H, d, J ═ 8Hz), 7.01(1H, brd, J ═ 8Hz), 7.20-7.31(5H, m), 7.36(1H, brs), 7.51(1H, d, J ═ 8Hz), 8.07(1H, d, J ═ 8Hz) ms (esi) m/z: 438(M +1) preparation of methyl 130-33- (2-chloro-4-ethylthiomethylphenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate and methyl 1- (2-chloro-4-ethylthiomethylphenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate

According to the same manner as in preparation example 14-2, from methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.57g), pale yellow crystals of methyl 3- (2-chloro-4-ethylthiomethylphenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.21g) and amorphous methyl 1- (2-chloro-4-ethylthiomethylphenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (947mg) were obtained.

3- (2-chloro-4-ethylsulfanylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester mp 116- ¹H-NMR(CDCl₃)：1.31(3H，t，J＝7.5Hz)，2.54(3H，s)，2.92(2H，q，J＝7.5Hz)，4.00(3H，s)，5.63(2H，s)，6.55(1H，d，J＝8Hz)，7.01(1H，dd，J＝8，1Hz)，7.34(1H，d，J＝1Hz)，8.05(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz)MS(ESI)m/z：376(M+1).

1- (2-chloro-4-ethylsulfanylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester mp 150-¹H-NMR(CDCl₃): 1.32(3H, t, J ═ 7.5Hz), 2.66(3H, s), 2.93(2H, q, J ═ 7.5Hz), 4.02(3H, s), 5.39(2H, s), 6.41(1H, d, J ═ 8Hz), 7.02(1H, dd, J ═ 8.1Hz), 7.36(1H, d, J ═ 1Hz), 7.55(1H, d, J ═ 8Hz), 8.07(1H, d, J ═ 8Hz) ms (esi) m/z: 376(M +1) preparation 131-13- [ 2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine 5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- [ 2-chloro-4- (n-pentylthio) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) was obtained as colorless crystalsProduct of (9) (182 mg). mp 178 + 179 deg.C¹H-NMR(DMSO-d₆): 0.83(3H, t, J ═ 7.5Hz), 1.19-1.41(4H, m), 1.49-1.62(2H, m), 2.51(3H, s), 2.97(2H, t, J ═ 7.5Hz), 5.57(2H, s), 6.50(1H, d, J ═ 8Hz), 7.14(1H, dd, J ═ 8.1Hz), 7.46(1H, d, J ═ 1Hz), 8.00(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) ms (esi) m/z: 404(M +1) preparation 131-23- [ 4- (phenylmethylthio) -2-chloro ] benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same method as in preparation example 4-7, methyl 3- [ 4- (benzylthio) -2-chloro ] benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (462mg) was used to give the desired product (413mg) as colorless crystals. mp 177-¹H-NMR(DMSO-d₆): 2.48(3H, s), 4.25(2H, s), 5.55(2H, s), 6.49(1H, d, J ═ 8Hz), 7.13-7.39(6H, m), 7.50(1H, d, J ═ 1Hz), 8.00(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) ms (esi) m/e: 424(M +1) preparation 131-33- (2-chloro-4-ethylsulfanylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- (2-chloro-4-ethylthiomethylphenyl-methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.2g) was used to give the desired product (1.07g) as colorless crystals. mp 202-¹H-NMR(DMSO-d₆): 1.21(3H, t, J ═ 7.5Hz), 2.52(3H, s), 2.99(2H, q, J ═ 7.5Hz), 5.57(2H, s), 6.50(1H, d, J ═ 8Hz), 7.15(1H, dd, J ═ 8.1Hz), 7.47(1H, d, J ═ 1Hz), 8.00(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) ms (esi) m/z: 360(M-1) preparation of methyl 132-13- (2-chloro-4- ((3-pyridyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate

According to the same manner as in example 118 described below, from methyl 3- (2-chloro-4- ((methanesulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (300mg) and 3-hydroxypyridine (77mg), the objective product (197mg) was obtained as pale yellow crystals. ¹H-NMR(CDCl₃)：2.55(3H，s)，4.00(3H，s)，5.06(2H，s)，5.69(2H，s)，6.65(1H，d，J＝8Hz)，7.16(1H, d, J ═ 8Hz), 7.19-7.30(2H, m), 7.55(1H, s), 8.07(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz), 8.21-8.19(1H, m), 8.36(1H, s) ms (esi) m/e: 423.1(M + H). preparation 132-23- (2-chloro-4- ((3-pyridyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- ((3-pyridyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (210mg) gave the desired product (162mg) as pale yellow crystals.¹H-NMR(DMS0-d₆): 2.52(3H, s), 5.17(2H, s), 5.63(2H, s), 6.59(1H, d, J ═ 8Hz), 7.26-7.36(2H.m), 7.43(1H, dd, J ═ 8.2Hz), 7.68(1H, s), 8.01(1H, d, J ═ 8Hz), 8.10-8.20(2H, m), 8.34(1H, d, J ═ 2Hz) ms (esi) m/e: 407.2(M-H) preparation of methyl 133-13- (4- (N-butyrylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate

According to the same method as in preparation example 133-2, from methyl 3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (500mg) and benzenesulfonyl chloride (191mg), the desired product (510mg) was obtained as colorless crystals.¹H-NMR(CDCl₃): 0.94(3H, t, J ═ 7Hz), 1.64-1.78(2H, m), 2.32(2H, t, J ═ 8Hz), 2.48(3H, s), 3.98(3H, s), 5.48(2H, s), 6.17(1H, d, J ═ 8Hz), 7.04(1H, dd, J ═ 8.2Hz), 7.86(1H, s), 8.07(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz), 8.67(1H, s) preparative examples 133-23- (4- (N-benzoylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

Triethylamine (110mg) was added to a solution of methyl 3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (300mg) in methylene chloride (3 ml). Benzoyl chloride (134mg) was added under ice-bath conditions, and the mixture was stirred at room temperature for 12 hours. Water was added thereto, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Hexane was added to the residue to crystallize it, which was collected by filtration and dried under reduced pressure to give the desired product (317mg) as colorless crystals¹H-NMR(CDCl₃): 2.50(3H, s), 3.49(3H, s), 5.55(2H, s), 6.35(1H, d, J ═ 8Hz), 7.17(1H, d, J ═ 8Hz), 7.37-7.53(3H, m), 7.89(2H, d, J ═ 8Hz), 8.06-8.17(3H, m), 8.70(1H, s) preparation 134-13- (4- (N-butyrylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4- (N-butyrylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (239mg) gave the desired product (228mg) as colorless crystals.¹H-NMR(DMSO-d₆): 0.89(3H, t, J ═ 7Hz), 1.52-1.63(2H, m), 2.26(2H, t, J ═ 7Hz), 2.50(3H, s), 5.56(2H, s), 6.57(1H, d, J ═ 8Hz), 7.28(1H, dd, J ═ 8.2Hz), 7.97-8.02(2H, m), 8.12(1H, d, J ═ 8Hz) preparation 134-23- (4- (N-benzoylamino) -2-chlorobenzyl-methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (4- (N-benzoylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) was used to give the desired product (165mg) as colorless crystals.¹H-NMR(DMSO-d₆): preparation of 135-13- (4- (N-benzoyl-N-methylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester 2.52(3H, s), 5.60(2H, s), 6.63(1H, d, J ═ 8Hz), 7.50-7.62(4H, m), 7.92-8.15(5H, m)

To a solution of methyl 3- (4- (N-benzoylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (300mg) in N, N-dimethylformamide (3ml) was added 60% sodium hydride (oily, 30.4mg) at room temperature, and after 15 minutes, methyl iodide (108mg) was added. After stirring at room temperature for 2 hours, ice water was poured in and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. Concentration under reduced pressure gave the desired product (305mg) as a pale yellow powder.¹H-NMR(CDCl₃)：2.45(3H，s)，3.45(3H，s)，4.00(3H，s)，5.59(2H，s)，6.51(1H，d，J＝8Hz)，Preparation example 135-23- (4- (N-benzoyl-N-methylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine 5-carboxylic acid (1H, d, J ═ 8Hz), 7.18-7.25(6H, m), 8.03(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 4-7, methyl 3- (4- (N-benzoyl-N-methylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (288mg) was used to give the desired product (257mg) as a pale yellow powder.¹H-NMR(DMSO-d₆): 2.40(3H, s), 2.50(3H, s), 5.55(2H, s), 6.51(1H, d, J ═ 8Hz), 7.01(1H, dd, J ═ 8.2Hz), 7.22 to 7.32(5H, m), 7.49(1H, s), 7.98(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz), preparation 136-13- (4- (N-butyryl-N-methylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation 135-1, methyl 3- (4- (N-butyrylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (250mg) and methyl iodide (97mg) were combined to give the desired product (107mg) as colorless crystals.¹H-NMR(CDCl₃): 0.85(3H, t, J ═ 7Hz), 1.56-1.64(2H, m), 2.06(2H, br), 2.58(3H, s), 3.22(3H, s), 4.00(3H, s), 5.69(2H, s), 6.68(1H, d, J ═ 8Hz), 6.94(1H, dd, J ═ 8.2Hz), 7.31(1H, s), 8.07(1H, d, J ═ 8Hz), 8.16(1H, d, J ═ 8Hz), preparation 136-23- (4- (N-butyryl-N-methylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation examples 4 to 7, methyl 3- (4- (N-butyryl-N-methylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (102mg) was used to give the objective product (99mg) as a pale yellow powder.¹H-NMR(DMSO-d₆): 0.77(3H, t, J ═ 7Hz), 1.39-1.51(2H, m), 2.03(2H, br), 2.53(3H, s), 3.13(3H, s), 5.64(2H, s), 6.57(1H, d, J ═ 8Hz), 7.17(1H, d, J ═ 8Hz), 7.64(1H, s), 8.01(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz), preparation 137-13- (2-chloro-4- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-Carboxylic acid methyl ester

According to the same manner as 83-4, from methyl 3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (500mg) and valeraldehyde (169mg), the desired product (481mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 0.91(3H, t, J ═ 7Hz), 1.30-1.40(4H, m), 1.55-1.63(2H, m), 2.55(3H, s), 3.00-3.06(2H, m), 3.73(1H, br), 4.01(3H, s), 5.57(2H, s), 6.31(1H, d, J ═ 8Hz), 6.55-6.60(2H, m), 8.03(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) preparation 137-23- (2-chloro-4- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- (N- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) was used to give the desired product (186mg) as a colorless powder.¹H-NMR(DMSO-d₆): 0.86(3H, t), 1.22-1.34(4H, m), 1.43-1.46(2H, m), 2.49(3H, s), 2.93(2H, m), 5.46(2H, s), 5.96(1H, br), 6.37-6.43(2H, m), 6.64(1H, d, J ═ 2Hz), 7.99(1H, d, J ═ 8Hz), 8.09(1H, d, J ═ 8Hz) preparation 137-33- (2-chloro-4- (N-methyl-N- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 85-1, from methyl 3- (2-chloro-4- (N- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (201mg) and 37% formaldehyde solution (151mg), the desired product (95mg) was obtained as a pale yellow powder.¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.20-1.38(4H, m), 1.46-1.56(2H, m), 2.85(3H, s), 2.91(3H, s), 3.26(2H, t, J ═ 7Hz), 4.05(3H, s), 5.72(2H, s), 6.43(1H, dd, J ═ 8.2Hz), 6.63(1H, d, J ═ 2Hz), 6.91(1H, d, J ═ 8Hz), 8.32(1H, d, J ═ 8Hz), 8.38(1H, d, J ═ 8Hz), preparative examples 137-43- (2-chloro-4- (N-methyl-N- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] carboxylic acid-5-pyridine-carboxylic acid

By the same method as in production examples 4 to 7, starting from 3- (2-chloro)Methyl (4- (N-methyl-N- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (85mg) gives the desired product as a pale yellow powder (50 mg).¹H-NMR(DMSO-d₆): 0.84(3H, t, J ═ 7Hz), 1.15-1.32(4H, m), 1.38-1.48(2H, m), 2.77(3H, s), 2.86(3H, s), 5.66(2H, s), 6.55(1H, dd, J ═ 8.2Hz), 6.71(1H, d, J ═ 2Hz), 6.90(1H, d, J ═ 8Hz), 8.27(1H, d, J ═ 8Hz), 8.40(1H, d, J ═ 8Hz), preparation 138-13- (4- (N-benzenesulfonylamino) -2-chlorobenzomethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

Pyridine (95.7mg) was added to a solution of methyl 3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) in methylene chloride (2 ml). Benzenesulfonyl chloride (117mg) was added under ice-bath conditions, and the mixture was stirred at room temperature for 12 hours. Water was added thereto, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Methanol was added to the residue to crystallize it, and the crystals were collected by filtration and dried under reduced pressure to give the desired product (213mg) as colorless crystals.¹H-NMR(CDCl₃): 2.45(3H, s), 3.99(3H, s), 5.57(2H, s), 6.45(1H, d, J ═ 8Hz), 6.83(1H, dd, J ═ 8.2Hz), 7.24(1H, d, J ═ 2Hz), 7.44(2H, t, J ═ 7Hz), 7.54(1H, t, J ═ 7Hz), 7.76 to 7.79(2H, m), 8.04(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz), preparation 138-23- (4- (N-benzenesulfonylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- (4- (N-benzenesulfonylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (200mg) was used to give the desired product (179mg) as colorless crystals.¹H-NMR(DMSO-d₆): 2.43(3H, s), 5.50(2H, s), 6.55(1H, d, J ═ 8Hz), 6.96(1H, dd, J ═ 8.2Hz), 7.22(1H, d, J ═ 2Hz), 7.52-7.62(3H, m), 7.74-7.77(2H, m), 7.98(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), preparation 139-15-bromo-3- (2-chloro-4- (isopropoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

To a solution of 5-bromo-3- (2-chloro-4-carboxyphenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (400mg) in N, N-dimethylformamide (4ml) were added potassium carbonate (218mg) and isopropyl iodide (197mg) in this order, and the mixture was stirred at room temperature for 24 hours. Water and ethyl acetate were added to separate the solution, and the organic layer was washed successively with water-saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Hexane was added to the residue, and the mixture was heated, cooled, and filtered to collect precipitated crystals. The crystals were dried under reduced pressure under heating to give a grayish brown crystalline desired product (394 mg).¹H-NMR(CDCl₃): 1.34(3H, s), 1.36(3H, s), 2.48(3H, s), 5.17-5.39(1H, m), 5.58(2H, s), 6.60(1H, d, J ═ 8Hz), 7.40(1H, d, J ═ 8Hz), 7.78(1H, d, J ═ 8.2Hz), 7.87(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 2Hz) preparation 139-25-bromo-3- (2-chloro-4- (cyclohexyloxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine

To a solution of 5-bromo-3- (2-chloro-4-carboxyphenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (525mg) in methylene chloride (5ml) were added oxalyl chloride (0.36ml) and N, N-dimethylformamide (0.03ml), and the mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. Methylene chloride (5ml) was added thereto and dissolved, and triethylamine (698mg), 4-dimethylaminopyridine (10mg) and cyclohexanol (1.38g) were sequentially added thereto under ice-water bath conditions, followed by stirring for 30 minutes under ice-bath conditions and stirring for 30 minutes at room temperature. Concentrating under reduced pressure, adding water and ethyl acetate, and separating. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and a saturated brine in this order, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Hexane (20ml) was added to the residue, and the mixture was heated, filtered to remove black insoluble matter, then cooled, and the precipitated crystals were collected by filtration. The crystals were dried under reduced pressure with heating to give the objective product (533mg) as colorless crystals.¹H-NMR(CDCl₃)：1.15-1.90(10H，m)，2.48(3H，s)，4.96-5.04(1H，m)，5.58(2H，s)，6.61(1H，d，J＝8Hz)，7.40(1H，d，J＝8Hz)，7.79(1H，dd，J＝8.2Hz)，7.86(1H，d，J＝8Hz)，8.10(1H，d，J＝2Hz)Mass(ESI)：m/z 464(M+H)⁺Preparation 140-13- (2-4- (isopropoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acids

The desired product (282mg) was obtained as a pale yellow powder from 5-bromo-3- (2-chloro-4- (isopropoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (370mg) according to the same method as in preparation 113-5. ¹H-NMR(DMSO-d₆): 1.29(3H, s), 1.31(3H, s), 2.52(3H, s), 5.06-5.18(1H, m), 5.69(2H, s), 6.72(1H, d, J ═ 8Hz), 7.78(1H, d, J ═ 8.2Hz), 8.00-8.03(2H, m), 8.15(1H, d, J ═ 8Hz) preparation 140-23- (2-chloro-4- (cyclohexyloxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

The same procedures used in preparation 113-5 were repeated except for using 5-bromo-3- (2-chloro-4- (cyclohexyloxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (514mg) to give the desired product (317mg) as colorless crystals.¹H-NMR(DMSO-d₆): preparation of example 141-13- (2-chloro-4- (3-phenylureido) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester 1.28-1.58(6H, m), 1.69(2H, brs), 1.83(2H, brs), 2.52(3H, s), 4.87-4.95(1H, m), 5.69(2H, s), 6.71(1H, d, J ═ 8Hz), 7.80(1H, dd, J ═ 8.2Hz), 8.01-8.03(2H, m), 8.05(1H, d, J ═ 8Hz)

Methyl 3- (4-amino-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (275mg) was suspended in toluene (10ml), and phenyl isocyanate (218mg) was added thereto at room temperature, followed by refluxing with heating for 5 hours. Concentrating under reduced pressure, adding hexane (20ml), heating, cooling, and filtering to collect precipitated crystal. The crystals were suspended in ethyl acetate (10ml), heated, allowed to cool, and the precipitated crystals were collected by filtration. The crystals were dried under reduced pressure with heating to give the desired product (328mg) as colorless crystals. ¹H-NMR(CDCl₃)：2.49(3H，s)，4.01(3H，s)，5.46(2H，s)，5.78(1H，d，J＝8Hz)，6.75(1H，d，J＝8Hz)，6.99(1H，t，J＝7Hz)，7.20-7.26(2H，m)，7.31-7.37(3H，m)，8.05(1H，s)，8.15(1H，d，J＝8Hz)，8.21(1H，d，J＝8Hz)，8.34(1H，s)Mass(ESI)：m/z 448(M-H)^-Preparation example 141-23- (2-chloro-4- (3-phenylureido) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- (3-phenylureido) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (300mg) was used to give the desired product (222mg) as a pale yellow powder.¹H-NMR(DMSO-d₆)：2.52(3H，s)，5.57(2H，s)，5.66(1H，d，J＝8Hz)，6.98(1H，t，J＝7Hz)，7.01(1H，dd，J＝8.2Hz)，7.28(2H，t，J＝8Hz)，7.43(2H，d，J＝8Hz)，7.89(1H，d，J＝2Hz)，8.01(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz)，8.72(1H，s)，8.93(1H，s)Mass(ESI)：m/z 434(M-H)^-Preparation example 142-14-acetoxy-2-chlorotoluene

Acetic anhydride (430mg) and pyridine (416mg) were added to a solution of 3-chloro-4-methylphenol (500mg) in diethyl ether (5.0ml), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was washed 1 time with 1N hydrochloric acid, 2 times with saturated brine, dried over magnesium sulfate, and concentrated and dried under reduced pressure to solidify the product, which was obtained as a pale yellow oil (645 mg).¹H-NMR(CDCl₃): preparation of 142-22-bromomethyl-5-acetoxy-chlorobenzene (1H, d), 2.36(3H, s), 6.90(1H, dd, J ═ 8, 2Hz), 7.12(1H, d, J ═ 2Hz), 7.22(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 93-1, 4-acetoxy-2-chlorotoluene (13.4g) was afforded the objective product (18.4g) as a pale yellow oil.¹H-NMR(CDCl₃): preparation of methyl 142-33- (4-acetoxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate, 2.30(3H, s), 4.58(2H, s), 7.02(1H, dd, J ═ 8.2Hz), 7.18(1H, d, J ═ 2Hz), 7.44(1H, d, J ═ 8Hz)

According to the same manner as in preparation example 14-2, from methyl 2-methylimidazo [ 4, 5-b ] pyridine-5-carboxylate (5.00g) and 2-bromomethyl-5-acetoxychlorobenzene (6.89g), the objective product (4.64g) was obtained as a pale brown powder.¹H-NMR(CDCl₃)：2.28(3H，s)，2.56(3H，s)，4.00(3H，s)，5.64(2H，s)，6.64(1H，d，J＝8Hz)，6.86(1H，dd，J＝8.2Hz)，7.24(1H，d，J＝2Hz)，8.06(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz)

The by-product obtained was 1- (4-acetoxy-2-chlorophenylmethyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (3.84g) as a pale brown powder.¹H-NMR(CDCl₃): preparation 142-43- (2-chloro-4-hydroxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (2.30 (3H, s), 2.68(3H, s), 4.02(3H, s), 5.43(2H, s), 6.48(1H, d, J ═ 8Hz), 6.88(1H, dd, J ═ 8, 2Hz), 7.28(1H, d, J ═ 2Hz), 7.56(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz)

To a mixture of methyl 3- (4-acetoxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.87g), methanol (29ml), 1, 4-dioxane (29ml) and water (2.9ml) was added sodium hydrogencarbonate (968mg), and the mixture was stirred at room temperature for 2.5 hours. Then, 1, 4-dioxane (29ml) was added thereto to dissolve the insoluble matter, and after stirring for 2 hours, sodium hydrogencarbonate (968mg) was added thereto, and the mixture was stirred at room temperature for 2 days, at 60 ℃ for 3 hours, and then allowed to stand overnight. The reaction mixture was partitioned with ethyl acetate and water, and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried, concentrated and dried under reduced pressure to solidify, and the residue was pulverized in diethyl ether to give the desired product (1.94g) as a pale yellow powder ¹H-NMR(DMSO-d₆): 2.52(3H, s), 3.86(3H, s), 5.50(2H, s), 6.50(1H, d, J ═ 8Hz), 6.64(1H, dd, J ═ 8, 2Hz), 6.92(1H, d, J ═ 2Hz), 8.04(1H, d, J ═ 8Hz), 8.16(1H, d, J ═ 8Hz), 10.00(1H, brs) preparation 143-12-methyl-5-ethoxychlorobenzene

The same procedures used in preparation 74-2 were repeated except for using 3-chloro-4-methylphenol (3.0g) to give the desired product (3.56g) as a pale yellow oil.¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 6Hz), 2.28(3H, s), 4.00(3H, q, J ═ 6Hz), 6.72(1H, dd, J ═ 8, 2Hz), 6, 90(1H, d, J ═ 2Hz), 7.10(1H, d, J ═ 8Hz), preparative examples 143-22-bromomethyl-5-ethoxychlorobenzene

The same procedures used in preparation 93-1 were repeated except for using 2-methyl-5-ethoxychlorobenzene (3.56g) to give the objective product (3.99g) as a pale yellow oil.¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 6Hz), 4.02(3H, q, J ═ 6Hz), 4.59(2H, s), 6.78(1H, dd, J ═ 8, 2Hz), 6.92(1H, d, J ═ 2Hz), 7.32(1H, d, J ═ 8Hz), preparation 144-13- [ 2-chloro-4-propoxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 74-2, methyl 3- [ 2-chloro-4-hydroxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (240mg) gave the desired product (220mg) as colorless crystals. ¹H-NMR(CDCl₃): 1.01(3H, t, J ═ 7Hz), 1.70-1.85(2H, m), 2.53(3H, s), 3.86(2H, t, J ═ 7Hz), 4.00(3H, s), 5.61(2H, s), 6.63(2H, s), 6.96(1H, brs), 8.04(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) mass (esi): m/z 374(M +1) preparation 144-23-2-chloro-4- (n-pentyloxy) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 74-1, methyl 3- [ 2-chloro-4-hydroxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (240mg) was used to give the desired product (247mg) as colorless crystals.¹H-NMR(CDCl₃): 0.92(3H, brt, J ═ 7Hz), 1.29-1.48(4H, m), 1.69-1.81(2H, m), 2.53(3H, s), 3.89(2H, t, J ═ 7Hz), 4.00(3H, s), 5.61(2H, s), 6.63(2H, s), 6.96(1H, brs), 8.04(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) masks (esi): m/z 402(M +1) preparation of methyl 144-33- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate and methyl 1- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate

According to the same manner as in preparation example 14-2, methyl 2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (554mg) gave 3- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (380mg) as pale yellow crystals, and amorphous methyl 1- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (415 mg).

3- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃)：1.39(3H，t，J＝7Hz)，2.53(3H，s)，3.93-4.03(5H，m)，5.62(2H，s)，6.63(1H，s)，6.64(1H，s)，6.96(1H，brs)，8.05(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz)Mass(ESI)：m/z 360(M+1).

1- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 7Hz), 2.66(3H, s), 3.94-4.04(5H, m), 5.37(2H, s), 6.49(1H, d, J ═ 8Hz), 6.68(1H, dd, J ═ 8, 2Hz), 6.99(1H, d, J ═ 2Hz), 7.54(1H, d, J ═ 8Hz), 8.06(1H, d, J ═ 8Hz) mass esi (esi): m/z 360(M +1) preparation 144-43- (2-chloro-4- (2-methoxyethoxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in preparation example 74-1, methyl 3- (2-chloro-4-hydroxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (240mg) gave the desired product (216mg) as colorless crystals.¹H-NMR(CDCl₃): 2.53(3H, s), 3.43(3H, s), 3.69-3.74(2H, m), 4.00(3H, s), 4.04-4.09(2H, m), 5.62(2H, s), 6.63(1H, d, J ═ 8Hz), 6.69(1H, dd, J ═ 8, 2Hz), 7.01(1H, d, J ═ 2Hz), 8.05(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz) masks (esi): m/z 390(M +1) preparation 144-53- [ 2-chloro-4- [ (thien-2-yl) methyl ] oxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 14-2, methyl 3- [ 2-chloro-4-hydroxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (240mg) gave the desired product (220mg) as colorless crystals.¹H-NMR(CDCl₃)：2.53(3H，s)，4.00(3H，s)，5.17(2H，s)，5.61(2H，s)，6.64(1H, d, J ═ 8Hz), 6.73(1H, dd, J ═ 8, 2Hz), 6.99(1H, dd, J ═ 8.5Hz), 7.05-7.10(2H, m), 7.32(1H, d, J ═ 5Hz), 8.05(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz) masks (esi): m/z 428(M +1) preparation 144-63- [ 2-chloro-4- [ (thien-3-yl) methyl ] oxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

Diethyl azodicarboxylate (139mg) was added to a suspension of methyl 3- [ 2-chloro-4-hydroxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (240mg), 3-thiophenemethanol (68mg) and triphenylphosphine (218mg) in dry dichloromethane in an ice bath. After 2 hours the reaction was stirred at room temperature. After 6 hours, diethyl azodicarboxylate (69mg) was added to a suspension of 3-thiophenemethanol (34mg) and triphenylphosphine (109mg) in dry dichloromethane under ice-bath conditions. After 20 hours, the reaction mixture was subjected to flash silica gel column chromatography (silica gel 60ml), eluted with chloroform and then recrystallized from ethyl acetate to give the desired product (143mg) as colorless crystals. ¹H-NMR(CDCl₃): 2.54(3H, s), 4.00(3H, s), 5.02(2H, s), 5.62(2H, s), 6.64(1H, d, J ═ 8Hz), 6.72(1H, dd, J ═ 8.2Hz), 7.05(1H, d, J ═ 2Hz), 7.12(1H, brd, J ═ 5Hz), 7.26-7.38(2H, m), 8.05(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz) masss (esi): m/z 428(M +1) preparation 144-73- [ 2-chloro-4-cyclopentylmethoxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 74-2, methyl 3- [ 2-chloro-4-hydroxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (240mg) gave the desired product (83mg) as a colorless amorphous product.¹H-NMR(CDCl₃): 1.22-1.41(2H, m), 1.50-1.70(3H, m), 1.75-1.90(2H, m), 2.33(1H, m), 2.53(3H, s), 3.77(2H, d, J ═ 5Hz), 4.00(3H, s), 5.62(2H, s), 6.64(2H, s), 6.97(1H, brs), 8.05(1H, d, J ═ 8Hz), 8.14(1H, d, J ═ 8Hz) masks (esi): m/z 414(M +1) preparation 145-13- [ 2-chloro-4-propoxybenzylmethyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According toThe same procedures used in preparation examples 4 to 7 were repeated except for using methyl 3- [ 2-chloro-4-propoxybenzylmethyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (247mg) to give the desired product (205mg) as colorless crystals. ¹H-NMR(DMSO-d₆): 0.93(3H, t, J ═ 7Hz), 1.62 to 1.76(2H, m), 2.51(3H, s), 3.91(2H, t, J ═ 7Hz), 5.54(2H, s), 6.56(1H, d, J ═ 8Hz), 6.81(1H, dd, J ═ 8, 2Hz), 7.13(1H, d, J ═ 2Hz), 8.00(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz) masss (esi): m/z 358(M-1) preparation 145-23- [ 2-chloro-4- (n-pentyloxy) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- [ 2-chloro-4- (n-pentyloxy) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (247mg) was used to obtain the desired product (208mg) as colorless crystals.¹H-NMR(DMSO-d₆): 0.87(3H, t, J ═ 7Hz), 1.27-1.41(6H, m), 1.61-1.72(2H, m), 2.50(3H, s), 3.94(2H, t, J ═ 71Hz), 5.53(2H, s), 6.55(1H, d, J ═ 8Hz), 6.80(1H, dd, J ═ 8, 2Hz), 7.13(1H, d, J ═ 2Hz), 8.00(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz) mass (esi): m/z 386(M-1) preparation 145-33- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (376mg) was used to give the desired product (380mg) as colorless crystals. ¹H-NMR(DMSO-d₆): 1.21(3H, t, J ═ 7.5Hz), 2.52(3H, s), 2.99(2H, q, J ═ 7.5Hz), 5.57(2H, s), 6.50(1H, d, J ═ 8Hz), 7.15(1H, dd, J ═ 8, 1Hz), 7.47(1H, d, J ═ 1Hz), 8.00(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz), preparative examples 145-43- (2-chloro-4- (2-methoxyethoxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- (2-methoxyethoxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (216mg) was used to obtain the desired product (192mg) as colorless crystals.¹H-NMR(CDCl₃): 2.63(3H, s), 3.43(3H, s), 3.69-3.76(2H, m), 4.05-4.12(2H, m), 5.54(2H, s), 6.65(1H, d, J ═ 8Hz), 6.74(1H, dd, J ═ 8, 2Hz), 7.04(1H, d, J ═ 2Hz), 8.15(1H, d, J ═ 8Hz), 8.21(1H, d, J ═ 8Hz) masks (esi): m/z 374(M-1) preparation 145-53- [ 2-chloro-4- [ (thien-2-yl) methyl ] oxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, from methyl 3- [ 2-chloro-4- [ (thiophen-2-yl) methyl ] oxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (243mg), the desired product (195mg) was obtained as colorless crystals. ¹H-NMR(DMSO-d₆): 2.50(3H, s), 5.29(2H, s), 5.55(2H, brs), 6.57(1H, d, J ═ 8Hz), 6.90(1H, dd, J ═ 8.2Hz), 7.02(1H, dd, J ═ 5.3Hz), 7.19(1H, d, J ═ 3Hz), 7.27(1H, d, J ═ 2Hz), 7.55(1H, d, J ═ 5Hz), 8.00(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz) mass (esi): m/z 412(M-1) preparation 145-63- [ 2-chloro-4- [ (thien-3-yl) methyl ] oxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, methyl 3- [ 2-chloro-4- [ (thien-3-yl) methyl ] oxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (140mg) was used to give the desired product (118mg) as colorless crystals.¹H-NMR(DMSO-d₆): 2.50(3H, s), 5.09(2H, s), 5.55(2H, s), 6.57(1H, d, J ═ 8Hz), 6.89(1H, dd, J ═ 8.2Hz), 7.15(1H, d, J ═ 5Hz), 7.24(1H, d, J ═ 2Hz), 7.51-7.60(2H, m), 8.00(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz) mass (esi): m/z 412(M-1) preparation 145-73- [ 2-chloro-4- (cyclopentylmethoxy) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- [ 2-chloro-4-cyclopentylmethoxybenzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (82mg) gave the desired product (72mg) as colorless crystals. ¹H-NMR(CDCl₃)：1.24-1.41(2H，m)，1.50-1.70(3H，m)，1.75-1.90(2H, m), 2.33(1H, m), 2.64(3H, s), 3.79(2H, d, J ═ 5Hz), 5.53(2H, s), 6.67(1H, d, J ═ 8Hz), 6.70(1H, dd, J ═ 8, 2Hz), 7.00(1H, d, J ═ 2Hz), 8.15(1H, d, J ═ 8Hz), 8.21(1H, d, J ═ 8Hz) masks (esi): m/z 398(M-1) preparation 146-13- (2-chloro-4-iodobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in ester example 14-2, from methyl 2, 7-dimethylimidazo [ 4, 5-b ] pyridine-5-carboxylate (3.00g) and 2-chloro-4-iodobenzyl bromide (7.00g), the desired product (6.42g) was obtained as a white powder.¹H-NMR (DMSO): 2.51(3H, s), 2.63(3H, s), 3.85(3H, s), 5.50(2H, s), 6.30(1H, d, J ═ 8Hz), 7.58(1H, d, J ═ 8Hz), 7.88(1H, s), 7.95(1H, s) preparation 146-23- (2-chloro-4- (2-phenylvinyl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in preparation example 147-1, methyl 3- (2-chloro-4-iodobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (400mg) was used to give the desired product (386mg) as a white powder.¹H-NMR(CDCl₃): 2.54(3H, s), 2.75(3H, s), 3.99(3H, s), 5.67(2H, s), 6.56(1H, d, J ═ 8Hz), 7.21-7.72(7H), 7.99(1H, s) preparation 146-33- (2-chloro-4- (2-phenylvinyl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4- (2-phenylvinyl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (383mg) was used to obtain the desired product (348mg) as a white powder.¹H-NMR (DMSO): 2.48(3H, s), 2.61(3H, s), 5.60(2H, s), 6.52(1H, d, J ═ 8Hz), 7.34-7.60(6H), 7.76(1H, s), 7.85(1H, s) preparation of methyl 147-13- (2-chloro-4- (1-hexynyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate

Under nitrogen atmosphere at 60 deg.C, methyl 3- (2-chloro-4-iodobenzyl) -2-methyl 3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (2.31g), 1-hexyne (2.00g), palladium diacetateA mixture of (235mg), triphenylphosphine (549mg), copper (I) iodide (297mg), tributylamine (2.91g) and dimethylformamide (23ml) was stirred for 1.5 hours. The reaction mixture was partitioned with ethyl acetate and water, and the organic layer was washed with water, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate: 1 to 1: 2) to give the desired product (1.44g) as a gray powder.¹H-NMR(CDCl₃)：0.94(3H，t，J＝6Hz)，1.38-1.64(4H)，2.38(2H，t，J＝6Hz)，2.52(3H，s)，4.00(3H，s)，5.65(2H，s)，6.52(1H，d，J＝8Hz)，7.10(1H，d，J＝8Hz)，7.47(1H，s)，8.06(1H，d，J＝8Hz)，8.15(1H，d，J＝8Hz)

In addition, the by-product obtained was 3- (4-chloro-2- (1-hexynyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (288mg) as a gray powder. ¹H-NMR(CDCl₃): 0.94(3H, t, J ═ 6Hz), 1.35-1.65(4H), 2.38(2H, t, J ═ 6Hz), 2.65(3H, s), 4.00(3H, s), 5.67(2H, s), 6.56(1H, d, J ═ 8Hz), 7.12(1H, d, J ═ 8Hz), 7.47(1H, s), 8.15(1H, d, J ═ 8Hz), 8.35(1H, d, J ═ 8Hz), preparation 147-23- (2-chloro-4- (1-hexynyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

The desired product (872mg) was obtained as a gray powder from methyl 3- (2-chloro-4- (1-hexynyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.0g) by the same method as in preparation examples 4-7.¹H-NMR (DMSO): 0.86(3H, t, J ═ 6Hz), 1.30-1.54(4H), 2.38(2H, t, J ═ 6Hz), 2.48(3H, s), 5.58(2H, s), 6.47(1H, d, J ═ 8Hz), 7.20(1H, d, J ═ 8Hz), 7.54(1H, s), 7.98(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz), preparation 148-13- (2-chloro-4-cyclohexylmethoxybenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

The desired product (954mg) was obtained as colorless crystals from methyl 2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (513mg) and 2-chloro-1-chloromethyl-4-cyclohexylmethoxybenzene (751mg) according to the same method as in preparation example 102-5. ¹H-NMR(CDCl₃)：0.95-1.34(5H, m), 1.68-1.84(6H, m), 2.52(3H, s), 2.72(3H, s), 3.68(2H, d, J ═ 7Hz), 3.99(3H, s), 5.59(2H, s), 6.56-6.63(2H, m), 6.95(1H, d, J ═ 1Hz), 7.96(1H, s) ms (esi): m/z 442(M +1) preparation 148-23- (2-chloro-4-cyclohexylmethoxybenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, from methyl 3- (2-chloro-4-cyclohexylmethoxybenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (900mg), the desired product (797mg) was obtained as colorless crystals.¹H-NMR(CDCl₃): 0.97-1.35(5H, m), 1.67-1.85(6H, m), 2.63(3H, s), 2.75(3H, s), 3.71(2H, d, J ═ 7Hz), 5.50(2H, s), 6.58-6.70(2H, m), 6.98-6.99(1H, m), 8.03(1H, s) ms (esi): m/z 426(M-1) preparation 149-13- (2-chloro-4-vinylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 11-1, from methyl 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (1.10g) and tributyl (vinyl) tin (853mg), the desired product (786mg) was obtained.¹H-NMR(CDCl₃): 2.53(3H, s), 2.73(3H, s), 3.98(3H, s), 5.29(1H, d, J ═ 10Hz), 5.64(2H, s), 5.72(1H, d, J ═ 15Hz), 6.54(1H, d, J ═ 7Hz), 6.60(1H, dd, J ═ 10, 15Hz), 7.11(1H, d, J ═ 8Hz), 7.47(1H, d, J ═ 1Hz), 7.97(1H, s) ms (esi): m/z 356(M +1) preparation 149-23- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in preparation 67-4, methyl 3- (2-chloro-4-vinylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (750mg) gave the desired product (502mg) as colorless crystals.¹H-NMR(CDCl₃)：1.19(3H，t，J＝7Hz)，2.53(3H，s)，2.59(2H，q，J＝7Hz)，2.73(3H，s)，3.98(3H，s)，5.63(2H，s)，6.50(1H，d，J＝8Hz)，6.91(1H，d，J＝8Hz)，7.26(1H，overlapped with CDCl₃)，7.97(1H，s)MS(ESI)：m/z 358(M+1) Preparation example 149-33- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation 4-7, from methyl 3- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (490mg), the desired product (385mg) was obtained as colorless crystals.¹H-NMR(CDCl₃): 1.21(3H, t, J ═ 7Hz), 2.61(2H, q, J ═ 7Hz), 2.62(3H, s), 3.76(3H, s), 5.54(2H, s), 6.54(1H, d, J ═ 8Hz), 6.96(1H, d, J ═ 8Hz), 7.30(1H, s), 8.04(1H, s) ms (esi): m/z 342(M-1) preparation 150-13- (2-chloro-4-trifluoromethylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same manner as in preparation example 102-5, methyl 2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (467mg) and 1-bromomethyl-2-chloro-4-trifluoromethylbenzene gave the objective product (819mg) as pale yellow crystals.¹H-NMR(CDCl₃): 2.54(3H, s), 2.74(3H, s), 3.98(3H, s), 5.69(2H, s), 6.68(1H, d, J ═ 8Hz), 7.35(1H, brd, J ═ 8Hz), 7.70(1H, brs), 7.98(1H, s) preparation 150-23- (2-chloro-4-trifluoromethylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4-trifluoromethylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (767mg) was used to obtain the desired product (566mg) as pale yellow crystals.¹H-NMR(CDCl₃): preparation of 151-13- (2-chloro-4-ethoxybenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester (2.61) (3H, s), 2.78(3H, s), 5.61(2H, s), 6.67(1H, d, J ═ 8Hz), 7.41(1H, brd, J ═ 8Hz), 7.76(1H, brs), 8.08(1H, s)

According to the same manner as in preparation example 102-5, methyl 2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (430mg) and 1-bromomethyl-2-chloro-4-ethoxybenzene gave the desired product (631mg) as milky white crystals.¹H-NMR(CDCl₃)：1.38(3H，t，J＝7Hz)，2.53(3H，s)，2.73(3H, s), 3.97(2H, q, J ═ 7Hz), 3.99(3H, s), 5.59(2H, s), 6.59(1H, d, J ═ 8Hz), 6.64(1H, dd, J ═ 8, 2Hz), 6.95(1H, d, J ═ 2Hz), 7.97(1H, s) preparation 151-23- (2-chloro-4-ethoxybenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same manner as in preparation example 4-7, methyl 3- (2-chloro-4-ethoxybenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (621mg) was used to obtain the desired product (530mg) as colorless crystals. ¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 7Hz), 2.62(3H, s), 2.75(3H, s), 3.99(2H, q, J ═ 7Hz), 5.51(2H, s), 6.61(1H, d, J ═ 8Hz), 6.68(1H, dd, J ═ 8.2Hz), 6.99(1H, d, J ═ 2Hz), 8.03(1H, s) preparation 152-12- (2-chloro-4-phenylbenzyl) -6- (methoxycarbonyl) -3-methyl-2H-indazole

A mixture of 6- (methoxycarbonyl) -3-methyl-1H-indazole (1.90g), brominated 2-chloro-4-phenylbenzyl (3.37g), potassium carbonate (2.76g), ethyl acetate (10ml) and water (5ml) was stirred at 70 ℃ for 14 hours. Hexane and water were added, and the precipitated solid was collected by filtration and washed with a mixed solvent of ethyl acetate and hexane (2/3). This was dried under reduced pressure to obtain the desired product (1.02 g).¹H-NMR(CDCl₃δ ppm): 2.61(3H, s), 3.96(3H, s), 5.77(2H, s), 6.66(1H, d, J ═ 8.1Hz), 7.33 to 7.39(2H, m), 7.43(2H, t, J ═ 7.6Hz), 7.51(2H, d, J ═ 7.5Hz), 7.62 to 7.66(2H, m), 7.69(1H, d, J ═ 8.8Hz), 8.49(1H, s) preparation 152-26-carboxy-2- (2-chloro-4-phenylbenzyl) -3-methyl-2H-indazole

The desired product (1.80g) was obtained from 2- (2-chloro-4-phenylbenzyl) -6- (methoxycarbonyl) -3-methyl-2H-indazole (3.00g) according to the same method as in preparation example 39-6. This material was immediately used in the following reaction. Preparation example 153-13- (2-chloro-4-methylthiobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid methyl ester

According to the same method as in preparation example 102-5, from methyl 2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (648mg) and 2-chloro-1-chloromethyl-4-methylthiobenzene (76 mg)7mg) to give the objective product (904mg) as colorless crystals.¹H-NMR(CDCl₃): 2.45(3H, s), 2.53(3H, s), 2.73(3H, s), 3.99(3H, s), 5.61(2H, s), 6.53(1H, d, J ═ 8Hz), 6.95(1H, dd, J ═ 1.8Hz), 7.28(1H, d, J ═ 1Hz), 7.97(1H, s). ms (esi): m/z 376(M +1) preparation 153-23- (2-chloro-4-methylthiobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid

According to the same method as in preparation example 4-7, methyl 3- (2-chloro-4-methylthiobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylate (879mg) gave the desired product (797mg) as colorless crystals.¹H-NMR(CDCl₃): 2.46(3H, s), 2.62(3H, s), 2.76(3H, s), 5.52(2H, s), 6.55(1H, d, J ═ 8Hz), 6.99(1H, dd, J ═ 1.8Hz), 7.30(1H, d.J ═ 1Hz), 8.04(1H, s) ms (esi): m/z 360(M-1) example 1

3- (3, 4-Dichlorobenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (160mg) was dissolved in dry dimethylformamide (2ml), carbonyldiimidazole (111mg) was added, and the mixture was stirred at room temperature for 1 hour. To the reaction mixture were added n-pentylsulfonamide (108mg) and 1, 8-diazabicyclo [ 5, 4, 0 ] undec-7-ene (122mg), and the mixture was stirred at 100 ℃ for 1.5 hours. After the reaction mixture was cooled with ice, the solution was adjusted to pH4 with 1N hydrochloric acid, and separated with ethyl acetate and water. The organic layer was washed with water 2 times, dried over magnesium sulfate, concentrated and dried under reduced pressure to solidify. The residue was eluted with silica gel column chromatography (hexane: ethyl acetate 1: 1), and the obtained residue was crystallized from hexane-ethyl acetate to give 3- (3, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene (118 mg). ¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.20-1.51(4H，m)，1.75-1.93(2H，m)，2.52(3H，s)，3.47-3.63(2H，m)，4.16(2H，s)，6.98(1H，d，J＝8Hz)，7.16(1H，s)，7.32(1H，d，J＝8Hz)，7.70(1H，d，J＝8Hz)，7.89(1H，d，J＝8Hz)，8.01(1H，s)，8.59(1H，brs)Mass(ESI)：m/e 482(M-H)^-mp: 159 ℃ 160 ℃ example 2

According to the following examples3- (2, 3-Dichlorophenylmethyl) -2-methyl-5- (n-pentanesulfonylcarbamoyl) benzo [ b ] thiophene was obtained from 3- (2, 3-dichlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid in the same manner as in 1.¹H-NMR(CDCl₃)：0.86(3H，t，J＝7Hz)，1.22-1.49(4H，m)，1.74-1.92(2H，m)，2.48(3H，s)，3.48-3.61(2H，m)，4.27(2H，s)，6.56(1H，d，J＝8Hz)，6.99(1H，t，J＝8Hz)，7.33(1H，d，J＝8Hz)，7.71(1H，d，J＝8Hz)，7.89(1H，d，J＝8Hz)，7.90(1H，s)，8.45(1H，brs)Mass(ESI)：m/e 482(M-H)^-mp: 196 ℃ and 197 ℃ in example 3

According to the same manner as in example 1, from 3- (2, 5-dichlorobenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid, 3- (2, 5-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene was obtained.¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.22-1.48(4H，m)，1.76-1.92(2H，m)，2.49(3H，s)，3.48-3.62(2H，m)，4.21(2H，s)，6.61(1H，d，J＝2Hz)，7.13(1H，dd，J＝8 and 2Hz)，7.37(1H，d，J＝8Hz)，7.72(1H，dd，J＝8 and 2Hz)，7.90(1H，d，J＝8Hz)，7.93(1H，d，J＝2Hz)，8.52(1H，brs)Mass(ESI)：m/e 482(M-H)^-mp: 147 ℃ 148 ℃ example 4-1

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylpyrazolo [ 1, 5-a ] pyridine-5-carboxylic acid (102mg), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) pyrazolo [ 1, 5-a ] pyridine (103mg) was obtained as a yellow-green powder.¹H-NMR(CDCl₃): 0.88(3H, t, J ═ 7Hz), 1.24-1.46(4H, m), 1.84(2H, m), 2.38(3H, s), 3.54(2H, t, J ═ 7Hz), 4.13(2H, s), 6.79(1H, d, J ═ 8Hz), 7.09(1H, t, J ═ 8Hz), 7.43(1H, s), 7.87(1H, s), 8.43(1H, d, J ═ 8Hz), examples 4-2

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylpyrazolo [ 1, 5-a ] pyridine-5-carboxylic acid (101mg), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (benzenesulfonylcarbamoyl) pyrazolo [ 1 was obtained as a yellow powder, 5-a ] pyridine (139 mg).¹H-NMR(CDCl₃): 2.32(3H, s), 4.06(2H, s), 6.70(1H, d, J ═ 8Hz), 7.00-7.07(2H), 7.37(1H, s), 7.56(2H, t, J ═ 8Hz), 7.67(1H, t, J ═ 8Hz), 7.84(1H, s), 8.12(2H, d, J ═ 8Hz), 8.37(1H, d, J ═ 8Hz), example 5-1 Hz

According to the same manner as in example 1, from 1- (2, 4-dichlorobenzyl) -2-methylindolizine-7-carboxylic acid (200mg), 1- (2, 4-dichlorobenzyl) -2-methyl-7- (n-pentanesulfonylcarbamoyl) indolizine (208mg) was obtained as a yellow-green powder.¹H-NMR(CDCl₃): 0.88(3H, t, J ═ 6Hz), 1.23-1.45(4H), 1.82(2H, m), 2.14(3H, s), 3.53(2H, t, J ═ 6Hz), 4.17(2H, s), 6.68(1H, d, J ═ 8Hz), 6.86(1H, d, J ═ 8Hz), 7.06(1H, d, J ═ 8Hz), 7.42(1H, s), 7.82(1H, s), 7.86(1H, d, J ═ 8Hz), 8.51(1H, s)

According to the same manner as in example 1, from 1- (2, 4-dichlorobenzyl) -2-methylindolizine-7-carboxylic acid (200mg), 7- (n-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -2-methylindolizine (151mg) was obtained as a yellow-green powder.¹H-NMR(CDCl₃): 0.92(3H, t, J ═ 6Hz), 1.46(2H, m), 1.82(2H, m), 2.14(3H, s), 3.53(2H, t, J ═ 6Hz), 4.17(2H, s), 6.68(1H, d, J ═ 8Hz), 6.86(1H, d, J ═ 8Hz), 7.06(1H, d, J ═ 8Hz), 7.41(1H, s), 7.82(1H, s), 7.86(1H, d, J ═ 8Hz), 8.54(1H, s). examples 5-3

According to the same manner as in example 1, from 1- (2, 4-dichlorobenzyl) -2-methylindolizine-7-carboxylic acid (200mg), 1- (2, 4-dichlorobenzyl) -2-methyl-7- (benzenesulfonylcarbamoyl) indolizine (208mg) was obtained as a yellow-green powder.¹H-NMR(DMSO-d₆): 2.14(3H, s), 4.18(2H, s), 6.76(1H, d, J ═ 8Hz), 6.82(1H, d, J ═ 8Hz), 7.28(1H, d, J ═ 8Hz), 7.55-7.75(5H), 7.98(1H, d, J ═ 8Hz), 8.18(1H, d, J ═ 8Hz), 8.26(1H, s). example 6

In the same manner as in example 1, from 2-methyl-1- (4-phenylbenzyl) indolizine-7-carboxylic acid (3)00mg) to give 2-methyl-7- (n-pentylsulfonylcarbamoyl) -1- (4-phenylbenzyl) indolizine (329mg) as a yellow-green powder.¹H-NMR(DMSO-d₆): 0.83(3H, t, J ═ 6Hz), 1.29(2H, m), 1.38(2H, m), 1.70(2H, m), 2.17(3H, s), 3.52(2H, t, J ═ 6Hz), 4.18(2H, s), 6.92(1H, d, J ═ 8Hz), 6.82(1H, d, J ═ 8Hz), 7.27(2H, d, J ═ 8Hz), 7.33(1H, t, J ═ 8Hz), 7.43(2H, t, J ═ 8Hz), 7.52-7.64(5H), 8.20(1H, d, J ═ 8Hz), 8.44(1H, s). example 7, 7

From 4- (4-phenylbenzyl) quinoline-6-carboxylic acid (81mg), 6- (n-pentylsulfonylcarbamoyl) -4- (4-phenylbenzyl) quinoline (68mg) was obtained as a white powder in the same manner as in example 1.¹H-NMR(DMSO-d₆): 0.80(3H, t, J ═ 7Hz), 1.19-1.42(4H, br), 1.64-1.76(2H, br), 3.50(2H, br), 4.61(2H, s), 7.30-7.47(6H, m), 7.64(4H, m), 8.10(1H, d, J ═ 8Hz), 8.22(1H, d, J ═ 8Hz), 8.89-8.96(2H, m), example 8-1

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (115mg), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (98mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.28-1.50(4H, m), 1.80-1.95(2H, m), 2.66(3H, s), 3.49-3.59(2H, m), 5.55(2H, s), 6.69(1H, d, J ═ 8Hz), 7.20(1H, dd, J ═ 8, 1Hz), 7.51(1H, d, J ═ 1Hz), 8.17(1H, d, J ═ 8Hz), 8.22(1H, d, J ═ 8Hz), 9.77(1H, brs). mas (esi): m/z 467(M-1) mp 174-

The same procedures used in example 1 were repeated except for using 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (150mg) to give 5- (n-butylsulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (132mg) as colorless crystals. ¹H-NMR(CDCl₃)：0.94(3H，t，J＝7Hz)，1.42-1.54(2H，m)，1.80-1.92(2H，m)，2.62(3H，s)，3.51-3.60(2H，m)，554(2H, s), 6.67(1H, d, J ═ 8Hz), 7.19(1H, dd, J ═ 8.2Hz), 7.51(1H, d, J ═ 2Hz), 8.13(1H, d, J ═ 8Hz), 8.21(1H, d, J ═ 8Hz), 9.79(1H, brs) mas (esi): m/z 455(M +1) mp 153-

The same procedures used in example 1 were repeated except for using 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (150mg) to give 5-benzenesulfonylcarbamoyl-3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (128mg) as pale yellow crystals.¹H-NMR(CDCl₃): 2.61(3H, s), 5.55(2H, s), 6.69(1H, d, J ═ 8Hz), 7.21(1H, dd, J ═ 8.2Hz), 7.50-7.68(4H, m), 8.05(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), 8.17(2H, brd, J ═ 8Hz). mass (esi): m/z 475(M +1) mp 193-194 ℃ example 9

The same procedures used in example 1 were repeated except for using 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) to give 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (34mg) as pale yellow crystals.¹H-NMR(CDCl₃): 0.86(3H, t, J ═ 7Hz), 1.22-1.45(4H, m), 1.79-1.91(2H, m), 2.69(3H, s), 3.50-3.58(2H, m), 5.62(2H, s), 6.80(1H, d, J ═ 8Hz), 7.34-7.48(4H, m), 7.50-7.58(2H, m), 7.70(1H, brs), 8.14(1H, d, J ═ 8Hz), 8.20(1H, d, J ═ 8Hz), 9.83(1H, brs). mass (esi): m/z 509(M-1) mp 155-

According to the same manner as in example 1, from 3- (1-bromo-2-naphthyl) methyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (140mg), 3- (1-bromo-2-naphthyl) methyl-2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (40mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃)：0.84(3H，t，J＝7Hz)，1.22-1.44(4H，m)，1.74-1.87(2H，m)，2.65(3H，s)，3.46-3.55(2H，m)，5.81(2H，s)，6.81(1H，d，J＝8Hz)，7.57(1H，brt，J＝8Hz)，7.65(1H，brt，J＝8Hz)，7.74(1H，brd，J＝8Hz)，7.82(1H，brd，J＝8Hz)，8.13(1H，d，J＝8Hz), 8.20(1H, d, J ═ 8Hz), 8.39(1H, brd, J ═ 8Hz), 9.81(1H, brs). M/z 527(M-1) mp 200-

According to the same manner as in example 1, from 2-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (130mg), colorless crystals of 2-methyl-5- (n-pentylsulfonylcarbamoyl) -3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine (120mg) were obtained.¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.26-1.50(4H, m), 1.83-1.98(2H, m), 2.65(3H, s), 3.52-3.62(2H, m), 5.55(2H, s), 7.20(2H, d, J ═ 8Hz), 7.30-7.48(3H, m), 7.51-7.61(4H, m), 8.15(1H, d, J ═ 8Hz), 8.24(1H, d, J ═ 8Hz), 9.92(1H, brs). mas (esi): m/z 475(M-1) mp 170-

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (70mg), 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (66mg) was obtained as a white powder. ¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.24-1.50(4H，m)，1.78-1.94(2H，m)，2.63(3H，s)，3.49-3.60(2H，m)，5.53(2H，s)，6.60(1H，dd，J＝8 and 2Hz)，7.34(1H，d，J＝8Hz)，7.66(1H，d，J＝2Hz)，8.14(1H，d，J＝8Hz)，8.22(1H，d，J＝8Hz)，9.76(1H，brs)Mass(ESI)：m/e 511，513(M-H)^-mp: 183 ℃ 184 ℃ example 12-2

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (70mg), 3- (4-bromo-2-chlorophenylmethyl) -5- (n-butylsulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (63mg) was obtained as a white powder.¹H-NMR(CDCl₃)：0.93(3H，t，J＝7Hz)，1.39-1.56(2H，m)，1.78-1.92(2H，m)，2.64(3H，s)，3.50-3.61(2H，m)，5.53(2H，s)，6.61(1H，d，J＝8Hz)，7.34(1H，dd，J＝8 and 2Hz)，7.67(1H，d，J＝2Hz)，8.15(1H，d，J＝8Hz)，8.22(1H，d，J＝8Hz)，9.78(1H，brs)Mass(ESI)：m/e 497，499(M-H)^-mp: 165-166 ℃ example 12-3

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (70mg), 5- (benzenesulfonylcarbamoyl) -3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (68mg) was obtained as a white powder.¹H-NMR(CDCl₃)：2.62(3H，s)，5.53(2H，s)，6.65(1H，d，J＝8Hz)，7.37(1H，dd，J＝8 and 2Hz)，7.50-7.65(3H，m)，7.68(1H，d，J＝2Hz)，8.09(2H，s)，8.17(2H，m)，10.08(1H，brs)Mass(ESI)：m/e 517，519(M-H)^-mp: 193-

According to the same manner as in example 1, from 3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (81mg), 3- (2-bromo-4-chlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (70mg) was obtained as a pale yellow powder.¹H-NMR(CDCl₃)：0.89(3H，t，J＝7Hz)，1.22-1.50(4H，m)，1.79-1.95(2H，m)，2.68(3H，s)，3.48-3.61(2H，m)，5.54(2H，s)，6.62(1H，d，J＝8Hz)，7.23(1H，dd，J＝8 and 2Hz)，7.70(1H，d，J＝2Hz)，8.13-8.29(2H，m)，9.76(1H，brs)Mass(ESI)：m/e 511，513(M-H)^-mp: 167-

According to the same manner as in example 1, from 3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (79mg), 5- (benzenesulfonylcarbamoyl) -3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (56mg) was obtained as a pale yellow powder. ¹H-NMR(CDCl₃)：2.67(3H，s)，5.56(2H，s)，6.67(1H，d，J＝8Hz)，7.27(1H，dd，J＝8 and 2Hz)，7.50-7.68(3H，m)，7.71(1H，d，J＝2Hz)，8.07-8.22(4H，m)，10.06(1H，brs)Mass(ESI)：m/e 517，519(M-H)^-mp: 189-

By a method similar to example 1, from 3- (2-bromo-4-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (4)1mg) to give 3- (2-bromo-4-chlorophenylmethyl) -5- (n-butylsulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (27mg) as a pale yellow powder.¹H-NMR(CDCl₃)：0.94(3H，t，J＝7Hz)，1.38-1.56(2H，m)，1.76-1.93(2H，m)，2.67(3H，s)，3.48-3.62(2H，m)，5.55(2H，s)，6.62(1H，d，J＝8Hz)，7.24(1H，dd，J＝8 and 2Hz)，7.69(1H，d，J＝2Hz)，8.13-8.29(2H，m)，9.74(1H，brs)Mass(ESI)：m/e 497，499(M-H)^-mp: 145-146 ℃ example 14-1

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylindolizine-6-carboxylic acid (150mg), 3- (2, 4-dichlorobenzyl) -2-methyl-6- (n-pentanesulfonylcarbamoyl) indolizine (90mg) was obtained as a yellow-green powder.¹H-NMR(DMSO-d₆)：0.82(3H，t，J＝7Hz)，1.21-1.35(4H，m)，1.53-1.62(2H，m)，2.19(3H，s)，3.12-3.18(2H，m)，4.32(2H，s)，6.37(1H，s)，6.48(1H，d，J＝8Hz)，7.15(1H，d，J＝8Hz)，7.25(1H，dd，J＝8 and 3Hz)，7.32(1H，d，J＝8Hz)，7.66(1H，d，J＝3Hz)，8.34(1H，s)Mass(ESI)：m/e 465(M-H)^-Example 14-2

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylindolizine-6-carboxylic acid (150mg), 3- (2, 4-dichlorobenzyl) -2-methyl-6- (n-butylsulfonylcarbamoyl) indolizine (88mg) was obtained as a yellow-green powder.¹H-NMR(DMSO-d₆)：0.82(3H，t，J＝8Hz)，1.29-1.40(2H，m)，1.52-1.62(2H，m)，2.19(3H，s)，3.14-3.20(2H，m)，4.32(2H，s)，6.38(1H，s)，6.50(1H，d，J＝8Hz)，7.15(1H，d，J＝8Hz)，7.25(1H，dd，J＝8 and 3Hz)，7.32(1H，d，J＝8Hz)，7.66(1H，d，J＝3Hz)，8.37(1H，s)Mass(ESI)：m/e 451(M-H)^-Examples 14 to 3

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylindolizine-6-carboxylic acid (150mg), 3- (2, 4-dichlorobenzyl) -2-methyl-6- (benzenesulfonylcarbamoyl) indolizine (68mg) was obtained as a yellow-green powder.¹H-NMR(DMSO-d₆)：2.18(3H，s)，4.30(2H，s)，6.33(1H，s)，6.47(1H，d，J＝8Hz)，7.11(1H，d，J＝8Hz)，7.22-7.30(2H，m)，7.40-7.43(3H，m)，7.66(1H，s)，7.80-7.83(2H，m)，8.28(1H，s)Mass(ESI)：m/e 471(M-H)^-Example 15

The same procedures used in example 1 were repeated except for using 3- (2, 4-dichlorobenzyl) -2 ethyl-7-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (177mg) to give 3- (2, 4-dichlorobenzyl) -2-ethyl-7-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (211mg) as colorless crystals. ¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.29-1.50(7H, m), 1.80-1.95(2H, m), 2.76(3H, s), 2.87(2H, q, J ═ 7Hz), 3.50-3.60(2H, m), 5.53(2H, s), 6.67(1H, d, J ═ 8Hz), 7.15(1H, dd, J ═ 8, 2Hz), 7.51(1H, d, J ═ 2Hz), 8.02(1H, s), 9.82(1H, brs). masss (esi): m/e 495(M-1) mp: 178 ℃ and 180 ℃ example 16

According to the same manner as in example 1, from 2-ethyl-7-methyl-3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (120mg), colorless crystals of 2-ethyl-7-methyl-5- (n-pentylsulfonylcarbamoyl) -3- (4-phenylbenzyl) -3H-imidazo [ 4, 5-b ] pyridine (138mg) were obtained.¹H-NMR(CDCl₃): 0.87(3H, t, J ═ 7Hz), 1.25 to 1.47(7H, m), 1.80 to 1.92(2H, m), 2.75(3H, s), 2.90(2H, q, J ═ 7Hz), 3.50 to 3.59(2H, m), 5.52(2H, s), 7.15(1H, d, J ═ 8Hz), 7.28 to 7.47(3H, m), 7.50 to 7.59(4H, m), 8.02(1H, s) mass (esi): m/e 503(M-1) mp: 210 ℃ and 211 ℃ example 17-1

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (150mg), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (benzenesulfonylcarbamoyl) benzo [ b ] thiophene (117mg) was obtained as white crystals. ¹H-NMR(DMSO-d₆)：2.42(3H，s)，4.25(2H，s)，6.71(1H，d，J＝8Hz)，7.24(1H，dd，J＝2.8Hz)，7.60-7.78(5H，m)，7.97-8.04(3H，m)，8.11(1H，s)Mass(ESI)：488(M-H)^-Example 17-2

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (150mg), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-butylsulfonylcarbamoyl) benzo [ b ] thiophene (117mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：0.83(3H，t，J＝8Hz)，1.33-1.46(2H，m)，1.60-1.71(2H，m)，2.45(3H，s)，3.50(2H，t，J＝8Hz)，4.27(2H，s)，6.73(1H，d，J＝8Hz)，7.25(1H，dd，J＝2，8Hz)，7.67(1H，d，J＝2Hz)，7.83(1H，d，J＝8Hz)，8.08(1H，d，J＝8Hz)，8.18(1H，s)Mass(ESI)：468(M-H)^-Example 18

According to the same manner as in example 1, from 3- (4-phenylbenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (112mg), 3- (4-phenylbenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene (87mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：0.79(3H，t，J＝7Hz)，1.20-1.38(4H，m)，1.60-1.70(2H，m)，2.57(3H，s)，3.33-3.40(2H，m)，4.26(2H，s)，7.25-7.34(3H，m)，7.41(2H，t，J＝8Hz)，7.54-7.60(4H，m)，7.83(1H，d，J＝8Hz)，7.97(1H，d，J＝8Hz)，8.33(1H，s)Mass(ESI)：490(M-H)^-Example 19

According to the same manner as in example 1, from 3- (2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (120mg), 3- (2-chlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene (131mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：0.80(3H，t，J＝7Hz)，1.20-1.42(4H，m)，1.63-1.73(2H，m)，2.47(3H，s)，3.48(2H，t，J＝8Hz)，4.29(2H，s)，6.74(1H，d，J＝7Hz)，7.17(1H，t，J＝7Hz)，7.24(1H，t，J＝7Hz)，7.51(1H，d，J＝8Hz)，7.83(1H，d，J＝8Hz)，8.06(1H，d，J＝8Hz)，8.18(1H，s)Mass(ESI)：448(M-H)^-Example 20

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (212mg), 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl group was obtained as white crystals) Benzo [ b ] thiophene (137 mg).¹H-NMR(DMSO-d₆)：0.82(3H，t，J＝7Hz)，1.20-1.41(4H，m)，1.63-1.73(2H，m)，2.45(3H，s)，3.50(2H，t，J＝8Hz)，4.24(2H，s)，6.67(1H，d，J＝8Hz)，7.37(1H，dd，J＝2.8Hz)，7.78(1H，s)，7.82(1H，d，J＝8Hz)，8.08(1H，d，J＝8Hz)，8.17(1H，s)Mass(ESI)：528(M-H)^-Example 21

According to the same manner as in example 1, from 3- (2, 4-dichloro-5-fluorobenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (222mg), 3- (2, 4-dichloro-5-fluorobenzyl) -2-methyl-5- (n-pentanesulfonylcarbamoyl) benzo [ b ] thiophene (204mg) was obtained as white crystals. ¹H-NMR(DMSO-d₆)：0.80(3H，t，J＝8Hz)，1.22-1.40(4H，m)，1.03-1.73(2H，m)，2.48(3H，s)，3.51(2H，t，J＝8Hz)，4.27(2H，s)，6.70(1H，d，J＝8Hz)，7.83(1H，d，J＝8Hz)，7.88(1H，d，J＝7Hz)，8.08(1H，d，J＝8Hz)，8.17(1H，s)Mass(ESI)：500(M-H)^-Example 22

According to the same manner as in example 1, from 3- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (218mg), 3- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene (176mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：0.79(3H，t，J＝7Hz)，1.18-1.40(4H，m)，1.63-1.74(2H，m)，2.60(3H.s)，3.50(2H，t，J＝8Hz)，4.56(2H，s)，7.38(1H，t，J＝7Hz)，7.47(1H，t，J＝7Hz)，7.76(1H，d，J＝8Hz)，7.83(1H，d，J＝8Hz)，7.86(1H，d，J＝7Hz)，8.08(1H，d，J＝8Hz)，8.41(1H，s)Mass(ESI)：504(M-H)^-Example 23

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-yl) methyl-2-methylbenzo [ b ] thiophene-5-carboxylic acid (200mg), 3- (1-bromonaphthalen-2-yl) methyl-2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene (207mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：0.75(3H，t，J＝7Hz)，1.15-1.37(4H，m)，1.60-1.70(2H，m)，2.48(3H，s)，3.47(2H，t，J＝8Hz)，4.54(2H，s)，6.91(1H，d，J＝8Hz)，7.60(1H，t，J＝7Hz)，7.72(1H，t，J＝7Hz)，7.80(1H，d，J＝8Hz)，7.83(1H，d，J＝8Hz)，7.91(1H，d，J＝8Hz)，8.096(1H，d，J＝8Hz)，8.26(1H，s)，8.30(1H，d，J＝8Hz)Mass(ESI)：544(M-H)^-Example 24-1

According to the same manner as in example 1, from 1- (2, 4-dichlorobenzyl) -2-methyl-1H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid (120mg), 1- (2, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -1H-thieno [ 2, 3-d ] imidazole (112mg) was obtained as a pale yellow powder.¹H-NMR(CDCl₃)：0.88(3H，t，7Hz).1.27-1.47(4H，m)，1.78-1.88(2H，m)，2.57(3H，s)，3.50-3.54(2H，m)，5.30(2H，s)，6.69(1H，d，8Hz)，7.18(1H，d，8Hz)，7.38(1H，s)，7.46(1H，d，2Hz)Mass(ESI)：472(M-H)^-Example 24-2

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methyl-3H-thieno [ 2, 3-d ] imidazole-5-carboxylic acid (90mg), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-thieno [ 2, 3-d ] imidazole (77mg) was obtained as a white powder. ¹H-NMR(CDCl₃)：0.87(3H，t，8Hz)，1.25-1.43(4H，m)，1.68-1.85(2H，m)，2.60(3H，s)，3.32-3.53(2H，m)，5.27(2H，s)，7.38(2H，s)，7.48(1H，s)，7.84(1H，s)Mass(ESI)：472(M-H)^-Example 25

According to the same manner as in example 1, from 1- (2, 4-dichlorobenzyl) -2-methyl-1H-imidazo [ 4, 5-b ] pyridine-6-carboxylic acid (150mg), colorless crystals of 3- (2, 4-dichlorobenzyl) -2-methyl-6- (n-pentylsulfonylcarbamoyl) -1H-imidazo [ 4, 5-b ] pyridine (151mg) were obtained.¹H-NMR(DMSO-d₆): 0.82(3H, t, J ═ 7Hz), 1.20-1.42(4H, m), 1.64-1.78(2H, m), 2.55(3H, s), 3.51(2H, t, J ═ 7Hz), 5.65(2H, s), 6.60(1H, d, J ═ 8Hz), 7.34(1H, dd, J ═ 8, 2Hz), 7.76(1H, d, J ═ 2Hz), 8.44(1H, s), 8.90(1H, s) mas (esi): m/z 467(M-1) mp 103-

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylpyrrolo [ 3, 2-b ] pyridine-5-carboxylic acid (100mg), colorless crystals of 3- (2, 4-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) pyrrolo [ 4, 5-b ] pyridine (87mg) were obtained.¹H-NMR(CDCl₃): 0.88(3H, t, J ═ 7Hz), 1.27-1.49(4H, m), 1.81-1.95(2H, m), 2.50(3H, s), 3.49-3.57(2H, m), 4.19(2H, s), 7.14-7.22(2H, m), 7.39(1H, s), 7.65(1H, d, J ═ 8Hz), 7.94(1H, d, J ═ 8Hz), 8.32(1H, brs). mas (esi): m/z 466(M-1) mp 147-148 ℃ example 26-2

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methylpyrrolido [ 3, 2-b ] pyridine-5-carboxylic acid (60mg), colorless crystals of 3- (2, 4-dichlorobenzyl) -2-methyl-5- (benzenesulfonylcarbamoyl) pyrrolo [ 3, 2-b ] pyridine (70mg) were obtained.¹H-NMR(DMSO-d₆): 2.39(3H, s), 4.25(2H, s), 7.29(1H, d, J ═ 8Hz), 7.33(1H, d, J ═ 8Hz), 7.58-7.74(5H, m), 7.79(1H, d, J ═ 8Hz), 8.04(1H, d, J ═ 8Hz), mass (esi): m/z 472(M-1) mp > 250 ℃ EXAMPLE 27

The same procedures used in example 1 were repeated except for using 3- (4-chloro-2-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (50mg) to give 3- (4-chloro-2-methoxybenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (47mg) as colorless crystals.¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.28-1.50(4H, m), 1.81-1.94(2H, m), 2.78(3H, s), 3.51-3.60(2H, m), 3.86(3H, s), 5.47(2H, s), 6.84-6.95(3H, m), 8.19(1H, d, J ═ 8Hz), 8.23(1H, d, J ═ 8Hz), 9.79(1H, brs). mas (esi): m/z 463(M-1) mp 168-

The same procedures used in example 1 were repeated except for using 3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (70mg) to give 3- (4-chloro-2-methylbenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (73mg) as colorless crystals. ¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.28-1.49(4H, m), 1.79-1.95(2H, m), 2.42(3H, s), 2.69(3H, s), 3.51-3, 60(2H, m), 5.45(2H, s), 6.43(1H, d, J ═ 8Hz), 7.09(1H, brd, J ═ 8Hz), 7.28(1H, brs), 8.17(1H, d, J ═ 8Hz), 8.23(1H, d, J ═ 8Hz), 9.78(1H, brs). mass (esi): m/z 447(M-1) mp 155-

According to the same manner as in example 1, from 3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (70mg), 5-benzenesulfonylcarbamoyl-3- (4-chloro-2-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (85mg) was obtained as colorless crystals.¹H-NMR(DMSO-d₆): 2.40(3H, s), 2.42(3H, s), 5.72(2H, s), 6.60(1H, d, J ═ 8Hz), 7.17(1H, brd, J ═ 8Hz), 7.39(1H, brs), 7.59-7.77(3H, m), 7.89(1H, d, J ═ 8Hz), 8.02(2H, brd, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), mass (esi): m/z 453(M-1) mp 235-

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (130mg), 5-benzenesulfonylcarbamoyl-3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (78mg) was obtained as colorless crystals. ¹H-NMR(CDCl₃)：2.40(3H，s)，2.76(3H，s)，5.64(2H，s)，6.95(1H，d，J＝8Hz)，7.38-7.52(4H，m)，7.59(2H，d，J＝8Hz)，7.82(1H，brs)，8.07-8.16(3H，m).MASS(ESI)：m/z 515(M-1)mp 204-214℃[broad]Example 29-2

The same procedures used in example 1 were repeated except for using 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (130mg) to give 5- (n-pentylsulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (106mg) as colorless crystals.¹H-NMR(CDCl₃)：0.90(3H，t，J＝7Hz)，1.38-1.51(2H，m)，1.77-1.89(2H，m)，2.75(SH，s)，3.50-3.59(2H，m)，5.65(2H，s)，6.89(1H，brd，J＝8Hz)，7.35-7.49(4H，m)，7.55(2H，brd，J＝8Hz)，7.71(1H，brs), 8.20(1H, d, J ═ 8Hz), 8.26(1H, d, J ═ 8Hz), 9.80(1H, brs). M/z 495(M-1) mp 199-

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (300mg, 0.90mmol), N' -carbonyldiimidazole (218mg, 1.34mmol), 1, 8-diazabicyclo [ 5, 4, 0 ] -7-undecene (DBU, 204mg, 1.34mmol) and 1-N-pentanesulfonamide (203mg, 1.34mmol), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (1-N-pentanesulfonylcarbamoyl) benzo [ b ] furan (260mg, 62%) was obtained as colorless crystals. mp: 149.1-149.9 ℃.¹H-NMR(DMSO-d₆，δppm)：11.94(1H，brs)，7.99(1H，d，J＝1.3Hz)，7.82(1H，dd，J＝1.7 and 8.6Hz)，7.63(1H，d，J＝2.1Hz)，7.61(1H，d，J＝8.6Hz)，7.33(1H，dd，J＝2.1 and 8.3Hz)，7.19(1H，d，J＝8.4Hz)，4.09(2H，s)，3.48(2H，m)，2.41(3H，s)，1.67(2H，quint.，J＝7.7Hz)，1.35(2H，quint.，J＝7.4Hz)，1.25(2H，sextet，J＝7.6Hz)，0.80(3H，t，J＝7.3Hz).IR(Nujol)：1687cm^-1Mass (fd): m/e 467(M). Example 30-2

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (220mg, 0.66mmol), N' -carbonyldiimidazole (160mg, 0.66mmol), DBU (150mg, 0.98mmol) and benzenesulfonamide (155mg, 0.98mmol), colorless crystals of 5- (benzenesulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (168mg, 54%) were obtained. mp: 208.5-209.5 ℃. ¹H-NMR(DMSO-d₆，δppm)：12.45(1H，brs)，7.97(2H，m)，7.93(1H，d，J＝1.6Hz)，7.75(1H，dd，J＝1.8 and 8.6Hz)，7.70(1H，m)，7.62(3H，m)，7.57(1H，d，J＝8.6Hz)，7.32(1H，dd，J＝2.1 and 8.3Hz)，7.16(1H，d，J＝8.4Hz)，4.06(2H，s)，2.38(3H，s).IR(Nujol)：1702cm^-1Mass (fd): m/e 473(M) example 31-1

In the same manner as in example 1, from 7-carboxy-2- (2, 4-dichlorobenzyl) -3, 5-dimethylbenzo [ b ] furan (0.30g),N, N' -carbonyldiimidazole (0.28g), DBU (0.26ml) and 1-N-pentanesulfonamide (0.26g) were added to give 2- (2, 4-dichlorobenzyl) -3, 5-dimethyl-7- (1-N-pentanesulfonylcarbamoyl) benzo [ b ] furan (0.26g) as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.79(3H，t，J＝7.2Hz)，1.20-1.28(2H，m)，1.30-1.37(2H，m)，1.64-1.71(2H，m)，2.19(3H，s)，2.42(3H，s)，3.46(2H，t，J＝7.7Hz)，4.24(2H，s)，7.33-7.38(2H，m)，7.46(1H，s)，7.59(1H，s)，7.62(1H，s)，11.57(1H，brs).IR(Nujol)：1691cm^-1Mass (fd): m/e 481(M) mp: 164-165.5 ℃ example 31-2

According to the same manner as in example 1, from 7-carboxy-2- (2, 4-dichlorobenzyl) -3, 5-dimethylbenzo [ b ] furan (0.30g), N' -carbonyldiimidazole (0.28g), DBU (0.26ml) and benzenesulfonamide (0.27g), 7- (benzenesulfonylcarbamoyl) -2- (2, 4-dichlorobenzyl) -3, 5-dimethylbenzo [ b ] furan (0.29g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：2.17(3H，s)，2.38(3H，s)，4.23(2H，s)，7.33-7.41(3H，m)，7.56(1H，s)，7.58-7.64(3H，m)，7.72(1H，t，J＝7.3Hz)，7.97-8.00(2H，m)，12.09(1H，brs).IR(Nujol)：1703cm^-1Mass (FD): m/e 487(M) mp: 214 ℃ 215 ℃ example 32-1

According to the same manner as in example 1, from 5-carboxy-2-methyl-3- (4-phenylbenzyl) benzo [ b ] furan (0.30g), N' -carbonyldiimidazole (0.28g), DBU (0.26ml) and 1-N-pentanesulfonamide (0.27g), 2-methyl-5- (1-N-pentanesulfonylcarbamoyl) -3- (4-phenylbenzyl) benzo [ b ] furan (0.25g) was obtained as white crystals. ¹H-NMR(DMSO-d₆，δppm)：0.79(3H，t，J＝7.3Hz)，1.21-1.26(2H，m)，1.34(2H，quint.，J＝7.5Hz)，1.67(2H，quint.，J＝7.7Hz)，2.51(3H，s)，3.49(2H，t，J＝7.7Hz)，4.07(2H，s)，7.32(1H，t，J＝7.3Hz)，7.36(2H，d，J＝8.1Hz)，7.42(2H，t，J＝7.6Hz)，7.57-7.62(5H，m)，7.82(1H，dd，J＝8.6 and 1.6Hz)，8.15(1H，s)，11.99(1H，brs)IR(Nujol)：1687cm^-1mp: 130.5-132 deg.C example 32-2

According to the same manner as in example 1, from 5-carboxy-2-methyl-3- (4-phenylbenzyl) benzo [ b ] furan (0.30g), N' -carbonyldiimidazole (0.28g), DBU (0.26ml) and 1-N-pentanesulfonamide (0.28g), 5- (1-benzenesulfonylcarbamoyl) -2-methyl-3- (4-phenylbenzyl) benzo [ b ] furan (0.31g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：2.49(3H，s)，4.04(2H，s)，7.30-7.35(3H，m)，7.42(2H，t，J＝7.7Hz)，7.54-7.63(7H，m)，7.69(1H，t，J＝7.4Hz)，7.74(1H，dd，J＝8.6 and 1.8Hz)，7.97-7.99(2H，m)，8.07(1H，d，J＝1.7Hz)，12.5(1H，brs).IR(Nujol)：1686cm^-1mp: 188-190 ℃ example 33-1

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (0.335g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 1-N-butylbenzamide (0.275g), 5- (1-N-butylsulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (0.26g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.85(3H，t，J＝7.4Hz)，1.34-1.42(2H，m)，1.61-1.68(2H，m)，2.42(3H，s)，3.49(2H，t，J＝8.3Hz)，4.09(2H，s)，7.19(1H，d，J＝8.4Hz)，7.33(1H，dd，J＝8.3 and 2.2Hz)，7.61(1H，d，J＝8.6Hz)，7.64(1H，d，J＝2.3Hz)，7.83(1H，dd，J＝8.7 and 1.9Hz)，7.99(1H，d，J＝1.7Hz)，11.95(1H，brs).IR(Nujol)：1698cm^-1mp: 145.5-146 ℃ example 33-2

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (0.335g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 1-N-hexylsulfonamide (0.33g), 3- (2, 4-dichlorobenzyl) -5- (1-N-hexylsulfonylcarbamoyl) -2-methylbenzo [ b ] furan (0.22g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.81(3H，t，J＝7.1Hz)，1.18-1.23(4H，m)，1.33-1.40(2H，m)，1.62-1.68(2H，m)，2.42(3H，s)，3.48(2H，t，J＝7.7Hz)，4.09(2H，s)，7.14(1H，d，J＝8.4Hz)，7.33(1H，dd，J＝8.3 and 2.2Hz)，7.61(1H，d，J＝8.6Hz)，7.64(1H，d，J＝2.2Hz)，7.82(1H，dd，J＝8.7 and 1.8Hz)，7.99(1H，d，J＝1.7Hz)，11.94(1H，brs).IR(Nujol)：1688cm^-1mp: 139-139.5 ℃ EXAMPLE 33-3

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (0.335g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 2-thiophenesulfonamide (0.33g), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (2-thiophenesulfonylcarbamoyl) benzo [ b ] furan (0.33g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：2.39(3H，s)，4.07(2H，s)，7.15-7.21(2H，m)，7.32(1H，dd，J＝8.3 and 2.3Hz)，7.58(1H，d，J＝8.6Hz)，7.63(1H，d，J＝2.2Hz)，7.78(1H，dd，J＝8.6 and 1.8Hz)，7.83(1H，dd，J＝3.7 and 1.1Hz)，7.95(1H，d，J＝1.6Hz)，8.02(1H，dd，J＝4.9 and 0.9Hz)，12.57(1H，brs).IR(Nujol)：1703cm^-1mp: 198-

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-ethylbenzo [ b ] furan (0.30g), N' -carbonyldiimidazole (0.26g), DBU (0.26ml) and 1-N-pentanesulfonamide (0.26g), 3- (2, 4-dichlorobenzyl) -2-ethyl-5- (1-N-pentanesulfonylcarbamoyl) benzo [ b ] furan (0.15g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.81(3H，t，J＝7.3Hz)，1.18(3H，t，J＝7.5Hz)，1.22-1.38(4H，m)，1.65-1.71(2H，m)，2.77(2H，quartet，J＝7.5Hz)，3.48(2H，t，J＝7.8Hz)，4.10(2H，s)，7.14(1H，d，J＝8.4Hz)，7.33(1H，dd，J＝8.4and 2.1Hz)，7.63-7.66(2H，m)，7.83(1H，dd，J＝8.8 and 1.9Hz)，8.01(1H，s)，11.95(1H，brs).IR(Nujol)：1689cm^-1mp: 131-

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-ethylbenzo [ b ] furan (0.335g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and benzenesulfonamide (0.33g), 5- (benzenesulfonylaminomethyl) was obtained as white crystalsAcyl) -3- (2, 4-dichlorobenzyl) -2-ethylbenzo [ b ] furan (0.26 g).¹H-NMR(DMSO-d₆，δppm)：1.16(3H，t，J＝7.6Hz)，2.75(2H，quartet，J＝7.6Hz)，4.08(2H，s)，7.12(1H，d，J＝8.4Hz)，7.32(1H，d，J＝8.4Hz)，7.58-7.65(4H，m)，7.70(1H，t，J＝7.0Hz)，7.76(1H，d，J＝8.8Hz)，7.96-7.99(3H，m)，12.46(1H，brs).IR(Nujol)：1704cm^-1mp: 196 ℃ C. & 197 ℃ C. example 34-3

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-ethylbenzo [ b ] furan (0.335g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 8-quinolinesulfonamide (0.33g), 3- (2, 4-dichlorobenzyl) -2-ethyl-5- (8-quinolinesulfonylcarbamoyl) benzo [ b ] furan (0.39g) was obtained as white crystals. ¹H-NMR(DMSO-d₆，δppm)：1.15(3H，t，J＝7.5Hz)，2.74(2H，quartet，J＝7.5Hz)，4.08(2H，s)，7.03(1H，d，J＝8.4Hz)，7.29(1H，dd，J＝8.3 and 2.1Hz)，7.54(1H，d，J＝8.7Hz)，7.59(1H，dd，J＝8.3 and 4.3Hz)，7.68(1H，d，J＝2.1Hz)，7.71(1H，dd，J＝8.7 and 1.6Hz)，7.82(1H，t，J＝7.8Hz)，7.99(1H，s)，8.34(1H，d，J＝8.0Hz)，8.51(2H，d，J＝7.8Hz).8.80(1H，dd，J＝4.2 and 1.6Hz).IR(Nujol)：1687cm^-1mp: 232 ℃ and 233 ℃ in example 34-4

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-ethylbenzo [ b ] furan (0.36g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 2-methylbenzenesulfonamide (0.31g), 3- (2, 4-dichlorobenzyl) -2-ethyl-5- ((2-methylbenzene) sulfonylcarbamoyl) benzo [ b ] furan (0.24g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：1.17(3H，t，J＝7.6Hz)，2.57(3H，s)，2.77(2H，quartet，J＝7.5Hz)，4.08(2H，s)，7.15(1H，d，J＝8.4Hz)，7.32(1H，dd，J＝8.3and 2.2Hz)，7.38(1H，d，J＝7.6Hz)，7.44(1H，t，J＝7.4Hz)，7.57(1H，t，J＝7.5Hz)，7.60(1H，d，J＝8.7Hz)，7.63(1H，d，J＝2.2Hz)，7.77(1H，d，J＝8.8Hz)，7.97(1H，s)，8.02(1H，d，J＝8.1Hz)，12.56(1H，brs).IR(Nujol)：1694cm^-1mp: 182 ℃ and 183 ℃ example 35-1

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-propylbenzo [ b ] furan (0.36g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 1-N-pentanesulfonamide (0.30g), 3- (2, 4-dichlorobenzyl) -5- (1-N-pentanesulfonylcarbamoyl) -2-propylbenzo [ b ] furan (0.36g) was obtained as white crystals.¹H-NMR(CDCl₃，δppm)：0.89(3H，t，J＝7.3Hz)，0.95(3H，t，J＝7.4Hz)，1.30-1.47(4H，m)，1.70-1.79(2H，m)，1.83-1.90(2H，m)，2.77(2H，t，J＝7.5Hz)，3.57(2H，t，J＝8.0Hz)，4.05(2H，s)，6.88(1H，d，J＝8.4Hz)，7.10(1H，dd，J＝8.3 and 2.2Hz)，7.45(1H，d，J＝2.1Hz)，7.50(1H，d，J＝8.6Hz)，7.71(1H，dd，J＝8.6 and 1.9Hz)，7.76(1H，d，J＝1.6Hz)，8.36(1H，brs).IR(Nujol)：1693cm^-1mp: 114-

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-propylbenzo [ b ] furan (0.36g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and benzenesulfonamide (0.31g), 5- (benzenesulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-propylbenzo [ b ] furan (0.24g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.83(3H，t，J＝7.4Hz)，1.56-1.63(2H，m)，2.70(2H，t，J＝7.4Hz)，4.08(2H，s)，7.10(1H，d，J＝8.4Hz)，7.32(1H，dd，J＝8.3and 2.2Hz)，7.58-7.65(4H，m)，7.70(1H，t，J＝7.4Hz)，7.76(1H，dd，J＝8.7and 1.8Hz)，7.96-7.99(3H，m)，12.45(1H，brs).IR(Nujol)：1708cm^-1mp: 197-197.5 ℃ examples 35-3

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-propylbenzo [ b ] furan (0.36g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 2-nitrobenzenesulfonamide (0.40g), 3- (2, 4-dichlorobenzyl) -5- (2-nitrobenzenesulfonylcarbamoyl) -2-propylbenzo [ b ] furan (0.18g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.84(3H，t，J＝7.3Hz)，1.58-1.64(2H，m)，2.72(2H，t，J＝7.4Hz)，4.09(2H，s)，7.13(1H，d，J＝8.3Hz)，7.32(1H，dd，J＝8.4and 2.2Hz)，7.61(1H，d，J＝8.7Hz)，7.63(1H，d，J＝2.0Hz)，7.82(1H，dd，J＝8.8 and 1.3Hz)，7.85-8.00(3H，m)，8.03(1H，s)，8.22-8.25(1H，m).IR(Nujol)：1692cm^-1mp: 219 ℃ 220 ℃ example 36

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) benzo [ b ] furan (0.26g), N' -carbonyldiimidazole (0.26g), DBU (0.24ml) and N-pentylsulfonamide (0.24g), 3- (2, 4-dichlorobenzyl) -5- (1-N-pentylsulfonylcarbamoyl) benzo [ b ] furan (0.24g) was obtained as a yellow oil.¹H-NMR(DMSO-d₆，δppm)：0.82(3H，t，J＝7.2Hz)，1.23-1.40(4H，m)，1.65-1.73(2H，m)，3.51(2H，t，J＝7.7Hz)，4.14(2H，s)，7.37(2H，s)，7.64(1H，s)，7.70(1H，d，J＝8.8Hz)，7.87(1H，s)，7.91(1H，dd，J＝8.7 and 1.6Hz)，8.269(1H，s)，12.01(1H，brs)IR(Nujol)：1682cm^-1Example 37

According to the same manner as in example 1, 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] thiophene (440mg, 1.25mmol) was suspended in dimethylformamide, and carbonyldiimidazole (305mg, 1.88mmol) was added thereto and the mixture was stirred at room temperature for 1 hour. 1-n-pentylsulfonamide (284mg, 1.88mmol) and DBU (286mg, 1.88ml) were then added, followed by stirring with heating at 100 ℃ for 15 hours. The reaction mixture was concentrated under reduced pressure, and water and 3N hydrochloric acid were added to the residue to adjust the mixture to acidity, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered to remove the drying agent, the filtrate was concentrated under reduced pressure, and the oily residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate 3/2), followed by recrystallization from 2-propanol-n-hexane to give 3- (2, 4-dichlorobenzyl) -2-methyl-5- (1-n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene (410mg, 68%) as colorless crystals. mp: 158.5-159.3 DEG C ¹H-NMR(DMSO-d₆，δppm)：12.01(1H，brs)，8.15(1H，d，J＝1.4Hz)，8.06(1H，d，J＝8.4Hz)，7.82(1H，dd，J＝1.6 and 8.4Hz)，7.66(1H，d，J＝2.1Hz)，7.25(1H，dd，J＝2.1 and 8.4Hz)，6.72(1H，d，J＝8.4Hz)，4.25(2H，s)，3.48(2H，m)，2.44(3H，s)，1.66(2H，quint.，J＝7.5Hz)，1.34(2H，quint.，J＝7.7Hz)，1.24(2H，sextet，J＝7.6Hz)，0.80(3H，t，J＝7.3Hz).IR(Nujol)：1661cm^-1Mass (FD): m/e 483(M) example 38-1

According to the same manner as in example 1, from 7-carboxy-2- (2, 4-dichlorobenzyl) -3-ethylbenzo [ b ] thiophene (0.25g), N' -carbonyldiimidazole (0.22g), DBU (0.20ml) and 1-N-pentanesulfonamide (0.21g), 2- (2, 4-dichlorobenzyl) -3-ethyl-7- (1-N-pentanesulfonylcarbamoyl) benzo [ b ] thiophene (0.24g) was obtained as white crystals.¹H-NMR(CDCl₃，δppm)：0.89(3H，t，J＝7.4Hz)，1.20(3H，t，J＝7.7Hz)，1.30-1.38(2H，m)，1.41-1.48(2H，m)，1.85-1.93(2H，m)，2.89(2H，quartet，J＝7.6Hz)，3.62(2H，t，J＝8.3Hz)，4.31(2H，s)，7.13(1H，d，J＝8.3Hz)，7.16(1H，dd，J＝8.4 and 2.0Hz)，7.41(1H，d，J＝2.2Hz)，7.49(1H，t，J＝7.8Hz)，7.62(1H，d，J＝7.5Hz)，7.96(1H，d，J＝7.9Hz)，8.4(1H，brs).IR(Nujol)：1667cm^-1Mass (FD): m/e 497(M) mp: 176-

According to the same manner as in example 1, from 7-carboxy-2- (2, 4-dichlorobenzyl) -3-ethylbenzo [ b ] thiophene (0.25g), N' -carbonyldiimidazole (0.22g), DBU (0.20ml) and benzenesulfonamide (0.22g), 7- (benzenesulfonylcarbamoyl) -2- (2, 4-dichlorobenzyl) -3-ethylbenzo [ b ] thiophene (0.15g) was obtained as white crystals.¹H-NMR(CDCl₃，δppm)：1.14(3H，t，J＝7.6Hz)，2.84(2H，quartet，J＝7.5Hz)，4.24(2H，s)，7.04(1H，d，J＝8.3Hz)，7.12(1H，dd，J＝8.3 and 2.0Hz)，7.38(2H，d，J＝2.0Hz)，7.54(2H，t，J＝7.7Hz)，7.62(1H，t，J＝7.4Hz)，7.70(1H，d，J＝7.5Hz)，7.87(1H，d，J＝7.9Hz)，8.18(2H，d，J＝7.9Hz).IR(Nujol)：1704cm^-1Mass (FD): m/e 503(M) mp: 181 ℃ and 183 ℃ example 39

According to example 1In the same manner, N-carbonyldiimidazole (0.290g) was added to a mixture of 6-carboxy-1- (2, 4-dichlorobenzyl) -3-methyl-2-benzimidazolone (0.314g) and N, N' -dimethylformamide (9ml), and the mixture was stirred at room temperature for 1 hour. After addition of 1-n-butanesulfonamide (0.246g) and DBU (0.273g), the mixture was stirred at 100 ℃ for 16 hours. The solvent was distilled off, and extracted with chloroform and water. The organic layer was concentrated, and the resulting residue was purified by thin layer chromatography to give 6- (1-n-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-methyl-2-benzimidazolone (0.123 g). ¹H-NMR(DMSO-d₆，δppm)：0.81(3H，t，J＝7.2Hz)，1.29(2H，m)，1.51(2H，m)，3.00(2H，m)，3.39(3H，s)，5.11(2H，s)，6.93(1H，d，J＝8.3Hz)，7.13(1H，d，J＝8.2Hz)，7.34(1H，d)，7.50(1H，s)，7.68(1H，s)，7.78(1H，d，J＝8.1Hz).IR(Nujol)：1666cm^-1mp: 358-360 ℃ Mass (FD): m/e 469(M) example 40

According to the same manner as in example 1, from 6-carboxy-1- (2, 4-dichlorobenzyl) -benzotriazole (0.12g), N' -carbonyldiimidazole (0.12g), DBU (0.11ml) and 1-N-butylbenzamide (0.10g), 6- (1-N-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) benzotriazole (0.13g) was obtained.¹H-NMR(CDCl₃.δppm)：0.90(3H，t，J＝7.4Hz)，1.40-1.48(2H，m)，1.76-1.82(2H，m)，3.57(2H，t，J＝8.4Hz)，5.93(2H，s)，6.89(1H，d，J＝8.4Hz)，7.13(1H，dd，J＝8.4 and 2.1Hz)，7.38(1H，d，J＝2.0Hz)，7.92(1H，d，J＝8.9Hz)，8.13(1H，d，J＝8.7Hz)，8.26(1H，s)，10.0(1H，brs).IR(Nujol)：1688cm^-1Mass (FD): m/e 440(M) mp: example 41-1 at 160 ℃ 158-

According to the same method as in example 1, 6-carboxy-1- (2, 4-dichlorobenzyl) -3-methyl-1H-indazole (0.44g, 1.31mmol) was dissolved in dimethylformamide (16ml), and N, N' -carbonyldiimidazole (319mg, 2.0mmol) was added and stirred at room temperature for 1 hour. Then, 1-n-butanesulfonamide (270mg, 2.0mmol) and DBU (300mg, 2.0mmol) were added thereto, and the mixture was stirred at 100 ℃ for 14 hours. Distilling under reduced pressure to remove dimethylformamide, adding 1N hydrochloric acid to the residue, and adjusting pHAfter 3 days, the precipitated oil was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the drying agent, and the filtrate was concentrated under reduced pressure. The oily residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate 1/1) to give 6- (1-n-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -1H-3-methylindazole (0.53g) as a crystalline oily substance. This material was recrystallized from ethyl acetate-hexane to give colorless crystals (0.36g, 60%). mp: 133.6-135.0 deg.C ¹H-NMR(CDCl₃，δppm)：8.82(1H，brs)，7.94(1H，s)，7.78(1H，d，J＝8.4Hz)，7.56(1H，d，J＝8.4Hz)，7.42(1H，d，J＝1.7Hz)，7.09(1H，dd，J＝1.9 and 8.4Hz)，6.63(1H，d，J＝8.4Hz)，5.64(2H，s)，3.58(2H，m)，2.62(3H，s)，1.83(2H，quint，J＝7.4Hz)，1.47(2H，sextet，J＝7.4Hz)，0.94(3H，t，J＝7.4Hz).IR(Nujol)：1681cm^-1Mass (FD): m/e 453(M) example 41-2

According to the same manner as in example 1, from 6-carboxy-1- (2, 4-dichlorobenzyl) -3-methyl-1H-indazole (0.335g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 1-pentanesulfonamide (0.30g), 1- (2, 4-dichlorobenzyl) -3-methyl-6- (1-pentanesulfonylcarbamoyl) -1H-indazole (0.39g) was obtained as pale yellow amorphous.¹H-NMR(DMSO-d₆，δppm)：0.82(3H，t，J＝7.2Hz)，1.22-1.40(4H，m)，1.66-1.74(2H，m)，2.51(3H，s)，3.52(2H，t，J＝7.7Hz)，5.69(2H，s)，6.78(1H，d.J＝8.4Hz)，7.34(1H，dd，J＝8.4 and 2.0Hz)，7.64(1H，d，J＝8.5Hz)，7.67(1H，d，J＝2.0Hz)，7.87(1H，d，J＝8.5Hz)，8.33(1H，s)，12.07(1H，brs).IR(Nujol)：1690cm^-1Examples 41 to 3

According to the same manner as in example 1, from 6-carboxy-1- (2, 4-dichlorobenzyl) -3-methyl-1H-indazole (0.335g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and benzenesulfonamide (0.31g), white crystalline 6- (benzenesulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-methyl-1H-indazole (0.36g) was obtained.¹H-NMR(DMSO-d₆，δppm)：2.50(3H，s)，5.68(2H，s)，6.75(1H，d，J＝8.5Hz)，7.33(1H，dd，J＝8.4 and 2.0Hz)，7.56(1H，d，J＝8.7Hz)，7.64(2H，t，J＝7.7Hz)，7.67(1H，d，J＝2.0Hz)，7.72(1H，t，J＝7.5Hz)，7.83(1H，d，J＝8.5Hz)，8.02(2H，d，J＝7.9Hz)，8.31(1H，s)，12.60(1H，brs).IR(Nujol)：1699cm^-1mp: 227.5-229 ℃ example 41-4

According to the same method as in example 1, from 6-carboxy-1- (2, 4-dichlorobenzyl) -3-methyl-1H-indazole (0.335g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and (E) - (2-phenylethene) sulfonamide (0.37g), white crystalline (E) -1- (2, 4-dichlorobenzyl) -3-methyl-6- ((2-phenylethenyl) sulfonylcarbamoyl) -1H-indazole (0.17g) was obtained.¹H-NMR(DMSO-d₆，δppm)：2.50(3H，s)，5.68(2H，s)，6.76(1H，d，J＝8.4Hz)，7.33(1H，dd，J＝8.4 and 2.2Hz)，7.43-7.47(3H，m)，7.53(1H，d，J＝15.4Hz)，7.64(1H，d，J＝8.5Hz)，7.67(1H，d，J＝15.5Hz)，7.76-7.79(2H，m)，7.85(1H，d，J＝8.4Hz)，8.34(1H，s)，12.35(1H，brs).IR(Nujol)：1694cm^-1mp: 209.5-210.5 deg.C example 42

According to the same manner as in example 1, from 7-carboxy-1- (2, 4-dichlorobenzyl) -3-ethyl-2, 4(1H, 3H) -quinazolinedione (0.79g), N' -carbonyldiimidazole (0.44g), DBU (0.41g) and 1-N-butylbenzamide (0.37g), 7- (1-N-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-ethyl-2, 4(1H, 3H) -quinazolinedione (0.58g) was obtained as white crystals. ¹H-NMR(DMSO-d₆，δppm)：0.81(3H，t，J＝7.4Hz)，1.18(3H，t，J＝7.2Hz)，1.32-1.40(2H，m)，1.61(2H，quint，J＝8.0Hz)，3.46(2H，t，J＝7.1Hz)，4.01(2H，quartet，J＝7.2Hz)，5.39(2H，s)，7.11(1H，d，J＝8.5Hz)，7.29(1H，d，J＝8.4Hz)，7.51(1H，s)，7.74(1H，d，J＝2.0Hz)，7.77(1H，d，J＝8.1Hz)，8.21(1H，d，J＝8.7Hz)，8.23(1H，s)，12.3(1H，brs).IR(Nujol)：1712，1693，1658cm^-1Mass (FD): m/e 511(M) mp: example 43 at 212 ℃ and 214 ℃

By the same method as in example 1, starting from 7-carboxy-3-, (2, 4-Dichlorophenylmethyl) -1-methyl-2, 4(1H, 3H) -quinazolinedione (0.57g), N' -carbonyldiimidazole (0.36g), DBU (0.34ml) and 1-N-butanesulfonamide (0.31g) gave 7- (1-N-butylsulfonylcarbamoyl) -3- (2, 4-dichlorophenylmethyl) -1-methyl-2, 4(1H, 3H) -quinazolinedione (0.65g) as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.88(3H，t，J＝7.4Hz)，1.39-1.46(2H，m)，1.70(2H，quint.，J＝7.7Hz)，3.56(2H，t，J＝7.9Hz)，3.60(3H，s)，5.14(2H，s)，7.18(1H，d，J＝8.4Hz)，7.30(1H，dd，J＝8.4 and 2.1Hz)，7.65(1H，d，J＝2.1Hz)，7.80(1H，d，J＝8.2Hz)，7.98(1H，s)，8.16(1H，d，J＝8.2Hz)，12.5(1H，brs).IR(Nujol)：1712，1693，1658cm^-1Mass (FD): m/e 497(M) mp: example 44 at 212 ℃ and 214 ℃

According to the same manner as in example 1, from 7-carboxy-3- (2, 4-dichlorobenzyl) -4(3H) -quinazolinone (0.35g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 1-N-butylbenzamide (0.27g), 7- (1-N-butylsulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -4(3H) -quinazolinone (0.38g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.87(3H，t，J＝7.6Hz)，1.38-1.46(2H，m)，1.66-1.73(2H，m)，3.54(2H，t，J＝7.8Hz)，5.25(2H，s)，7.21(1H，d，J＝8.4Hz)，7.38(1H，dd，J＝8.4 and 2.1Hz)，7.69(1H，d，J＝2.1Hz)，7.99(1H，dd，J＝8.3and 1.7Hz)，8.23(1H，d，J＝8.3Hz)，8.25(1H，d，J＝1.7Hz)，8.58(1H，s)，12.40(1H，brs).IR(Nujol)：1694cm^-1Mass (FD): m/e 468(M +1) mp: 245 ℃ and 247 ℃ example 45

According to the same manner as in example 1, from 7-carboxy-2- (2, 4-dichlorobenzyl) -3-methyl-4 (3H) -quinazolinone (0.19g), N' -carbonyldiimidazole (0.21g), DBU (0.20ml) and 1-N-butylbenzamide (0.20g), 7- (1-N-butylsulfonylcarbamoyl) -2- (2, 4-dichlorobenzyl) -3-methyl-4 (3H) -quinazolinone (0.09g) was obtained as white crystals. ¹H-NMR(CDCl₃，δppm)：0.96(3H，t，J＝7.4Hz)，1.48-1.53(2H，m)，1.84-1.91(2H，m)，3.58-3.62(5H，m)，4.29(2H，s)，7.14(1H，d，J＝8.3Hz)，7.23-7.26(1H，m)，7.50(1H，d，J＝2.1Hz)，7.89(1H，d，J＝8.3Hz)，7.97(1H，s)，8.36(1H，brs)，8.39(1H，d，J＝8.3Hz).IR(Nujol)：1690，1661cm^-1Mass (FD): m/e 482(M +1) mp: example 46 at 244 ℃ and 246 ℃

The same procedures used in example 1 were repeated except for adjusting the pH to 1 with 3N hydrochloric acid in the post-treatment step of the reaction to give 6- (1-N-butylsulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -3, 4-dihydro-2-methyl-quinazoline hydrochloride (0.16g) as pale yellow crystals from 6-carboxy-3- (2, 4-dichlorobenzyl) -3, 4-dihydro-2-methyl-quinazoline hydrochloride (0.27g), N' -carbonyldiimidazole (0.34g), DBU (0.31ml) and 1-N-butylbenzamide (0.29 g).¹H-NMR(DMSO-d₆，δppm)：0.82(3H，t，J＝7.4Hz)，1.27-1.33(2H，m)，1.48-1.56(2H，m)，2.43(3H，s)，3.04(2H，t，J＝7.7Hz)，4.72(2H，s)，4.86(2H，s)，7.01(1H，d，J＝8.3Hz)，7.49(1H，dd，J＝8.4 and 2.1Hz)，7.59(1H，d，J＝8.4Hz)，7.66(1H，s)，7.75(1H，d，J＝2.1Hz)，7.85(1H，d，J＝8.4Hz)，12.0(1H，brs).IR(Nujol)：1642cm^-1Mass (FD): m/e 467(M) mp: 258 deg.C (decomposition) example 47-1

According to the same manner as in example 1, from 7-carboxy-1- (2, 4-dichlorobenzyl) -2-methyl-4 (1H) -quinazolinone (0.36g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 1-N-pentanesulfonamide (0.24g), 1- (2, 4-dichlorobenzyl) -2-methyl-7- (1-N-pentanesulfonylcarbamoyl) -4(1H) -quinazolinone (0.47g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.80(3H，t，J＝7.3Hz)，1.18-1.26(2H，m)，1.29-1.35(2H，m)，1.60-1.67(2H，m)，2.67(3H，s)，3.48(2H，t，J＝8.3Hz)，5.70(2H，s)，7.14(1H，d，J＝8.6Hz)，7.33-7.36(1H，m)，7.83-7.86(2H，m)，8.07(1H，d，J＝8.4Hz)，8.33(1H，d，J＝8.3Hz).IR(Nujol)：1738，1694cm^-1Mass (FD): m/e 496(M +1) mp: 168-

In the same manner as in example 1 and from 7-carboxy-1- (2, 4-dichlorobenzyl) -2-methyl-4 (1H) -quinazolinone (0)36g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and benzenesulfonamide (0.31g) to give 7- (benzenesulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -2-methyl-4 (1H) -quinazolinone (0.50g) as white crystals. ¹H-NMR(CDCl₃，δppm)：2.66(3H，s)，5.68(2H，s)，7.11(1H，d，J＝8.5Hz)，7.31(1H，dd，J＝8.4 and 2.1Hz)，7.61(2H，t，J＝7.9Hz)，7.71(1H，t，J＝7.5Hz)，7.80(1H，s)，7.84(1H，d，J＝2.1Hz)，7.94(2H，d，J＝7.9Hz)，8.03(1H，d，J＝8.2Hz)，8.29(1H，d，J＝8.3Hz).IR(Nujol)：1735，1698cm^-1Mass (FD): m/e 502(M +1) mp: example 48 at 214-216 ℃

According to the same manner as in example 1, from 7-carboxy-1- (2, 4-dichlorobenzyl) -1, 4-dihydro-2-methyl-quinazolin 1/2 sulfate (0.100g), N' -carbonyldiimidazole (0.122g), DBU (0.11ml) and benzenesulfonamide (0.113g), white crystalline 1- (2, 4-dichlorobenzyl) -1, 4-dihydro-2-methyl-7- (1-N-pentanesulfonylcarbamoyl) quinazolin hydrochloride (0.075g) was obtained.¹H-NMR(DMSO-d₆，δppm)：0.79(3H，t，J＝7.3Hz)，1.18-1.34(4H，m)，1.55-1.65(2H，m)，2.43(3H，s)，3.40-3.50(2H，m)，4.86(2H.s)，5.30(2H，s)，7.27(1H，s)，7.37(1H，s)，7.38(1H，d，J＝2.0Hz)，7.41(1H，d，J＝8.2Hz)，7.79(1H，d，J＝1.9Hz)，7.81(1H，d，J＝7.9Hz)，11.4(1H，brs)，12.1(1H，brs).IR(Nujol)：1685cm^-1Mass (FD): m/e 482(M +1) mp: example 49 at 184-

According to the same manner as in example 1, from 7-carboxy-1- (2, 4-dichlorobenzyl) -3-methyl-2 (1H) -quinoxalinone (0.28g), N' -carbonyldiimidazole (0.23g), DBU (0.21ml) and 1-N-butylbenzamide (0.19g), 7- (1-N-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-methyl-2 (1H) -quinoxalinone (0.17g) was obtained.¹H-NMR(DMSO-d₆，δppm)：0.81(3H，t，J＝7.4Hz)，1.32-1.40(2H，m)，1.62(2H，quint，J＝7.5Hz)，2.51(3H，s)，3.47(2H，t，J＝7.5Hz)，5.48(2H，s).6.88(1H，d，J＝8.6Hz)，7.25(1H，dd，J＝8.5 and 2.3Hz)，7.69(1H，s)，7.75(1H，d，J＝2.3Hz)，7.86(1H，d，J＝8.4Hz)，7.90(1H，d，J＝8.3Hz)，12.2(1H，brs).IR(Nujol)：1708.1692cm^-1Mass (FD): m/e 481(M) mp: example 50 at 223-

According to the same manner as in example 1, from 7-carboxy-1- (2, 4-dichlorobenzyl) -4-methyl-2, 3(1H, 4H) -quinoxalinedione (0.28g), N' -carbonyldiimidazole (0.22g), DBU (0.20ml) and 1-N-butylbenzamide (0.18g), 7- (1-N-butylsulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -4-methyl-2, 3(1H, 4H) -quinoxalinedione (0.32g) was obtained. ¹H-NMR(DMSO-d₆，δppm)：0.80(3H，t，J＝7.3Hz)，1.30-1.38(2H，m)，1.60(2H，quint，J＝7.7Hz)，3.46(2H，t，J＝7.2Hz)，3.59(3H，s)，5.37(2H，s)，7.17(1H，d，J＝8.5Hz)，7.28(1H，dd，J＝8.5 and 2.2Hz)，7.45(1H，d，J＝1.8Hz)，7.58(1H，d，J＝8.8Hz)，7.75(1H，d，J＝2.1Hz)，7.86(1H，dd，J＝7.2 and 1.8Hz)，12.1(1H，brs).IR(Nujol)：1682cm^-1Mass (FD): m/e 497(M) mp: 243-

According to the same manner as in example 1, from 3-carboxy-4- (2, 4-dichlorobenzyl) -5-ethylimidazo [ 1, 2-b ] pyrazole (0.546g), N' -carbonyldiimidazole (0.524g), 1-N-pentanesulfonamide (0.488g) and DBU (0.491g), 4- (2, 4-dichlorobenzyl) -5-ethyl-3- (1-N-pentanesulfonylcarbamoyl) imidazo [ 1, 2-b ] pyrazole (0.140g) was obtained.¹H-NMR(CD30D，δppm)：0.77(3H，t，J＝7.1Hz)，1.11-1.27(7H，m)，1.58(2H，m)，2.45(2H，m)，3.26(2H，m)，5.78(2H，s)，6.43(1H，d，J＝8.4Hz)，7.12(1H，dd，J＝8.4 and 2.1Hz)，7.36(1H，s)，7.43(1H，d，J＝2.1Hz)，8.01(1H，s)IR(Nujol)：1661cm^-1Mass (FD): m/e 470(M) mp: 165-166.5 ℃ EXAMPLE 52

3- (2, 4-Dichlorobenzyl) -2-methyl-6- (1-N-pentanesulfonylcarbamoyl) imidazo [ 1- (2, 4-dichlorobenzyl) -2-methyl-6- (1-N-pentanesulfonylcarbamoyl) was obtained from a crude purified 6-carboxy-3- (2, 4-dichlorobenzyl) -2-methylimidazo [ 1, 2-a ] pyridine (0.40g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 1-N-pentanesulfonamide (0.31g) in the same manner as in example 12-a ] pyridine (0.07 g).¹H-NMR(DMSO-d₆，δppm)：0.81(3H，t，J＝7.2Hz)，1.21-1.37(4H，m)，1.61-1.68(2H，m)，2.26(3H，s)，3.33(2H，m)，4.44(2H，s)，6.86(1H，d，J＝8.1Hz)，7.30(1H，dd，J＝8.3 and 2.2Hz)，7.62(1H，d，J＝9.3Hz)，7.69(1H，d，J＝2.1Hz)，7.77(1H，brs)，8.84(1H，s).IR(Nujol)：1659cm^-1mp: 264 ℃ 267 ℃ example 53-1

From 4- (4-phenylphenoxy) -6-quinolinecarboxylic acid (227mg), 6- (n-pentylsulfonylcarbamoyl) -4- (4-phenylphenoxy) quinoline (91mg) was obtained as a brown powder in the same manner as in example 1.¹H-NMR(DMSO-d₆): 0.83(3H, t, J ═ 7Hz), 1.19-1.39(4H, br), 1.57-1.70(2H, br), 3.20(2H, br), 6.72(1H, d, J ═ 4Hz), 7.38-7.53(5H, m), 7.73(2H, d, J ═ 8Hz), 7.85(2H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz), 8.32(1H, d, J ═ 8Hz), 8.73(1H, d, J ═ 4Hz), 8.98(1H, s). examples 53-2

From 4- (4-phenylphenylmethoxy) -6-quinolinecarboxylic acid (600mg), 6- (n-pentylsulfonylcarbamoyl) -4- (4-phenylphenylmethoxy) quinoline (814mg) was obtained as a white powder in the same manner as in example 1.¹H-NMR(DMSO-d₆): 0.80(3H, t, J ═ 7Hz), 1.20-1.33(4H, br), 1.52-1.64(2H, br), 3.03-3.09(2H, m), 5.49(2H, s), 7.15(1H, d, J ═ 7Hz), 7.38(1H, m), 7.48(2H, m), 7.64-7.75(6H, m), 7.87(1H, d, J ═ 8Hz), 8.26(1H, d, J ═ 8Hz), 8.70(1H, d, J ═ 7Hz), 8.80(1H, s). example 54

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-ethylbenzo [ b ] furan (0.30g), N' -carbonyldiimidazole (0.28g), DBU (0.26ml) and 1-pentene-1-sulfonamide (0.30g), 3- (2, 4-dichlorobenzyl) -2-ethyl-5- (((E) -pentene-1-sulfonyl) carbamoyl) benzo [ b ] furan (0.24g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.86(3H，t，J＝7.4Hz)，1.18(3H，t，J＝7.5Hz)，1.40-1.48(2H，m)，2.23(2H，quartet，J＝7.0Hz)，2.77(2H，quartet，J＝7.5Hz)，4.09(2H，s)，6.76(1H，d，J＝15.2Hz)，6.83-6.90(1H，m)，7.13(1H，d，J＝8.4Hz)，7.33(1H，dd，J＝8.4 and 2.2Hz)，7.62(1H，d，J＝8.7Hz)，7.64(1H，d，J＝2.1Hz)，7.81(1H，dd，J＝8.8 and 1.8Hz)，7.99(1H，d，J＝1.6Hz)，12.05(1H，brs).IR(Nujol)：1657cm^-1mp: 191-192 ℃ example 55-1

According to the same manner as in example 1, from 6-carboxy-1- (2, 4-dichlorobenzyl) -3-ethyl-1H-indazole (0.35g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and 1-N-pentanesulfonamide (0.30g), 1- (2, 4-dichlorobenzyl) -3-ethyl-6- (1-N-pentanesulfonylcarbamoyl) -1H-indazole (0.47g) was obtained. ¹H-NMR(DMSO-d₆.δppm)：0.82(3H，t，J＝7.2Hz)，1.23-1.40(7H，m)，1.65-1.73(2H，m)，2.95(2H，quartet，J＝7.6Hz)，3.52(2H，t，J＝7.8Hz)，5.70(2H，s)，6.71(1H，d，J＝8.4Hz)，7.34(1H，dd，J＝8.4 and 2.1Hz)，7.64(1H，dd，J＝8.5 and 1.3Hz)，7.68(1H，d，J＝2.1Hz)，7.91(1H，d，J＝8.5Hz)，8.32(1H，s)，12.07(1H，brs).IR(Nujol)：1690cm^-1Example 55-2

According to the same manner as in example 1, from 6-carboxy-1- (2, 4-dichlorobenzyl) -3-ethyl-1H-indazole (0.35g), N' -carbonyldiimidazole (0.32g), DBU (0.30ml) and benzenesulfonamide (0.31g), 6- (benzenesulfonylcarbamoyl) -1- (2, 4-dichlorobenzyl) -3-ethyl-1H-indazole (0.38g) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆，δppm)：1.27(3H，t，J＝7.5Hz)，2.93(2H，quartet，J＝7.6Hz)，5.69(2H，s)，6.67(1H，d，J＝8.4Hz).7.33(1H，dd，J＝8.4 and 2.2Hz)，7.55(1H，dd，J＝8.5 and 1.3Hz)，7.64(2H，t，J＝7.4Hz)，7.68(1H，d，J＝2.1Hz)，7.72(1H，t，J＝7.4Hz)，7.87(1H，d，J＝8.5Hz)，8.01(2H，d，J＝7.8Hz)，8.28(1H，s)，12.55(1H，brs).IR(Nujol)：1697cm^-1mp: 208 ℃ 209 ℃ example 56

According to the same manner as in example 1, from a crude purified 6-carboxy-3- (2, 4-dichlorobenzyl) -2-methylimidazo [ 1, 2-a ] pyridine (0.20g) and NN' -carbonyldiimidazole (0.32g), DBU (0.30ml) and benzenesulfonamide (0.31g) to give 6- (benzenesulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylimidazo [ 1, 2-a ] pyridine (0.07g) as a brown solid. mp: 308 ℃ and 310 DEG C¹H-NMR(DMSO-d₆，δppm)：2.33(3H，s)，4.51(2H，s)，7.05(1H，d，J＝8.3Hz)，7.30(1H，dd，J＝8.4 and 2.1Hz)，7.56(2H，t，J＝7.6Hz)，7.60-7.63(1H，m)，7.71(1H，d，J＝2.2Hz)，7.87(1H，d，J＝8.4Hz)，7.94(2H，d，J＝7.2Hz)，8.09-8.14(1H，m)，8.98(1H，brs).IR(Nujol)：1664cm^-1Mass (FD): m/e 473(M) example 57-1

According to the same manner as in example 1, from 3- (2, 3-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (45mg), 3- (2, 3-dichlorobenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (32mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：0.79(3H，t，J＝8Hz)，1.19-1.40(4H，m)，1.65-1.75(2H，m)，2.51(3H，s)，3.52(2H，t，J＝8Hz)，5.86(2H，s)，6.60(1H，d，J＝8Hz)，7.27(1H，t，J＝8Hz)，7.62(1H，d，J＝8Hz)，8.01(1H，d，J＝8Hz)，8.22(1H，dd，J＝8Hz)Mass(ESI)：467(M-H)^-Example 57-2

According to the same manner as in example 1, from 3- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (78mg), pale yellow crystals of 3- ((3-chlorobenzo [ b ] thiophen-2-yl) methyl) -2-methyl-5- (n-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (47mg) were obtained. ¹H-NMR(DMSO-d₆)：0.79(3H，t，J＝8Hz)，1.22-1.41(4H，m)，1.68-1.78(2H，m)，2.63(3H，s)，3.57(2H，t，J＝8Hz)，6.13(2H，s)，7.43-7.58(2H，m)，7.80(1H，d，J＝8Hz)，7.92(1H，d，J＝8Hz)，8.03(1H，d，J＝8Hz)，8.20(1H，dd，J＝2.8Hz)Mass(ESI)：489(M-H)^-Example 58

The same procedures used in example 1 were repeated except for using 3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] thiophene-5-carboxylic acid (130mg),this gave 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (n-pentylsulfonylcarbamoyl) benzo [ b ] thiophene as white crystals (125 mg).¹H-NMR(DMSO-d₆)：0.78(3H，t，J＝7Hz)，1.17-1.38(4H，m)，1.60-1.72(2H，m)，2.47(3H，s)，3.49(2H，t，J＝8Hz)，6.81(1H，d，J＝8Hz)，7.32-7.48(4H，m)，7.65(2H，d，J＝8Hz)，7.80-7.86(2H，m)，8.08(1H，d，J＝8Hz)，8.23(1H，s)Mass(ESI)：524(M-H)^-Example 59

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (78mg), 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (((E) -1-pentene-1-sulfonyl) carbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (47mg) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆)：0.86(3H，t，J＝7Hz)，1.40-1.49(2H，m)，2.20-2.28(2H，m)，2.52(3H，s)，5.87(2H，s)，6.72-6.80(2H，m)，6.87-6.97(1H，m)，7.35-7.48(3H，m)，7.53(1H，d，J＝8Hz)，7.67(1H，d，J＝8Hz)，7.85(1H，s)，7.98(1H，dd，J＝2.8Hz)，8.19(1H，d，J＝8Hz)Mass(ESI)：507(M-H)^-Example 60-1

According to the same manner as in example 1, from 6-carboxy-1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (0.28g), N' -carbonyldiimidazole (0.32g), DBU (0.31ml) and 1-pentanesulfonamide (0.30g), 1- (2-chloro-4-phenylbenzyl) -3-methyl-6- (1-pentanesulfonylcarbamoyl) -1H-indazole (0.16g) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆，δppm)：0.81(3H，t，J＝7.3Hz)，1.22-1.30(2H，m)，1.32-1.39(2H，m)，1.66-1.73(2H，m)，2.53(3H，s)，3.52(2H，t，J＝7.7Hz)，5.75(2H，s)，6.84(1H，d，J＝8.2Hz).7.36-7.40(1H，m)，7.45(2H，t，J＝7.6Hz)，7.54(1H，dd，J＝8.0 and 1.9Hz)，7.64-7.67(3H，m)，7.78(1H，d，J＝1.9Hz)，7.88(1H，d，J＝8.3Hz)，8.38(1H，s)，12.09(1H，brs).IR(Nujol)：1684cm^-1mp: example 60-2 at 172-

By the same method as in example 1, from 6-carboxy-1- (2-chloro-4-phenylbenzyl)) -3-methyl-1H-indazole (0.25g), N' -carbonyldiimidazole (0.30g), DBU (0.30ml) and benzenesulfonamide (0.29g) to give 6- (benzenesulfonylcarbamoyl) -1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (0.17g) as pale yellow crystals. ¹H-NMR(DMSO-d₆，δppm)：2.51(3H，s)，5.73(2H，s)，6.80(1H，d，J＝8.1Hz)，7.36-7.40(1H，m)，7.45(2H，t，J＝7.7Hz)，7.53(1H，dd，J＝8.2 and 1.9Hz)，7.56(1H，dd，J＝8.6 and 1.2Hz)，7.60-7.68(3H，m)，7.69-7.74(1H，m)，7.78(1H，d，J＝1.8Hz)，7.84(1H，d，J＝8.9Hz)，7.99-8.02(2H，m)，8.34(1H，s)，12.57(1H，brs).IR(Nujol)：1702cm^-1mp: 211 ℃ and 212 ℃ examples 60-3

According to the same manner as in example 1, from 6-carboxy-1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (0.27g), N' -carbonyldiimidazole (0.32g), DBU (0.31ml) and (E) - (2-phenylethene) sulfonamide (0.37g), there was obtained (E) -1- (2-chloro-4-phenylbenzyl) -3-methyl-6- ((2-phenylethenyl) sulfonylcarbamoyl) -1H-indazole (0.25g) as pale yellow crystals.¹H-NMR(DMSO-d₆，δppm)：2.52(3H，s)，5.74(2H，s)，6.81(1H，d，J＝8.2Hz)，7.35-7.83(15H，m)，7.87(1H，d，J＝9.0Hz)，8.39(1H，s)，12.35(1H，brs).IR(Nujol)：1687cm^-1mp: 241 ℃ and 242 ℃ in example 60-4

According to the same manner as in example 1, from 6-carboxy-1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (0.22g), N' -carbonyldiimidazole (0.16g), DBU (0.15ml) and 1-pentene-1-sulfonamide (0.15g), 1- (2-chloro-4-phenylbenzyl) -3-methyl-6- (((E) -1-pentene-1-sulfonyl) carbamoyl) -1H-indazole (0.10g) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆，δppm)：0.86(3H，t，J＝7.4Hz)，1.42-1.48(2H，m)，2.21-2.27(2H，m)，2.53(3H，s)，5.74(2H，s)，6.77-6.83(2H，m)，6.87-6.92(1H，m)，7.38(1H，t，J＝7.3Hz)，7.45(2H，t，J＝7.6Hz)，7.54(1H，dd，J＝7.8 and2.1Hz)，7.61-7.67(3H，m)，7.79(1H，d，J＝1.8Hz)，7.87(1H，d，J＝8.5Hz)，8.35(1H，s)，12.20(1H，brs).IR(Nujol)：1682cm^-1mp: 201 ℃ and 202 DEG CExamples 60 to 5

According to the same manner as in example 1, from 6-carboxy-1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (0.25g), N' -carbonyldiimidazole (0.18g), DBU (0.18ml) and (4-vinylbenzene) sulfonamide (0.22g), 1- (2-chloro-4-phenylbenzyl) -3-methyl-6- ((4-vinylbenzene) sulfonylcarbamoyl) -1H-indazole (0.10g) was obtained as a pale yellow powder. ¹H-NMR(DMSO-d₆，δppm)：2.51(3H，s)，5.46(1H，d，J＝11.0Hz)，5.74(2H，s)，6.02(1H，d，J＝17.7Hz)，6.75-6.84(2H，m)，7.34-7.85(11H，m)，7.97(2H，d，J＝8.5Hz)，8.33(1H，s)，12.51(1H，brs).IR(Nujol)：1694cm^-1Examples 60 to 6

According to the same manner as in example 1, from 6-carboxy-1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (0.25g), N' -carbonyldiimidazole (0.18g), DBU (0.18ml) and (4-methylbenzene) sulfonamide (0.20g), white crystalline 1- (2-chloro-4-phenylbenzyl) -3-methyl-6- ((4-methylbenzene) sulfonylcarbamoyl) -1H-indazole (0.10g) was obtained.¹H-NMR(DMSO-d₆，δppm)：2.36(3H，s)，2.50(3H，s)，5.72(2H，s)，6.02(1H，d，J＝17.7Hz)，6.79(1H，d，J＝8.1Hz)，7.37-7.48(5H，m)，7.52(1H，d，J＝8.1Hz)，7.58(1H，d，J＝7.8Hz)，7，80(1H，d，J＝8.4Hz)，7.86(2H，d，J＝8.2Hz)，8.27(1H，s)，12.50(1H，brs).IR(Nujol)：1706cm^-1mp: 188-190 ℃ example 61-1

According to the same manner as in example 1, from 1- (4-bromo-2-chlorophenylmethyl) -6-carboxy-3-methyl-1H-indazole (0.25g), N' -carbonyldiimidazole (0.21g), DBU (0.20ml) and 1-pentanesulfonamide (0.20g), 1- (4-bromo-2-chlorophenylmethyl) -3-methyl-6- (1-pentanesulfonylcarbamoyl) -1H-indazole (0.25g) was obtained as pale yellow amorphous.¹H-NMR(DMSO-d₆，δppm)：0.82(3H，t，J＝7.2Hz)，1.24-1.40(4H，m)，1.67-1.73(2H，m)，2.51(3H，s)，3.52(2H，t，J＝7.7Hz)，5.67(2H，s)，6.71(1H，d，J＝8.3Hz)，7.46(1H，dd，J＝8.3 and 1.9Hz)，7.64(1H，d，J＝8.4Hz)，7.79(1H，d，J＝2.0Hz)，7.87(1H，d，J＝8.4Hz)，8.34(1H，s)，12.06(1H，brs).IR(Nujol)：1694cm^-1Example 61-2

According to the same manner as in example 1, from 1- (4-bromo-2-chlorophenylmethyl) -6-carboxy-3-methyl-1H-indazole (0.25g), N' -carbonyldiimidazole (0.21g), DBU (0.20ml) and benzenesulfonamide (0.21g), 6- (benzenesulfonylcarbamoyl) -1- (4-bromo-2-chlorophenylmethyl) -3-methyl-1H-indazole (0.19g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：2.50(3H，s)，5.66(2H，s)，6.67(1H，d，J＝8.3Hz)，7.46(1H，dd，J＝8.3 and 1.9Hz)，7.56(1H，d，J＝8.4Hz)，7.64(2H，brt，J＝6.6Hz)，7.71(1H，brd，J＝7.1Hz)，7.78(1H，d，J＝7.1Hz)，7.80-7.84(1H，m)，8.01(2H，d，J＝7.5Hz)，8.29(1H，s)，12.58(1H，brs).IR(Nujol)：1702cm^-1mp: 213-215 ℃ example 61-3

According to the same method as in example 1, from 1- (4-bromo-2-chlorophenylmethyl) -6-carboxy-3-methyl-1H-indazole (0.25g), N' -carbonyldiimidazole (0.21g), DBU (0.20ml) and (E) - (2-phenylethene) sulfonamide (0.24g), white crystalline (E) -1- (4-bromo-2-chlorophenylmethyl) -3-methyl-6- ((2-phenylvinyl) sulfonylcarbamoyl) -1H-indazole (0.18g) was obtained. ¹H-NMR(DMSO-d₆，δppm)：2.50(3H，s)，5.66(2H，s)，6.68(1H，d，J＝8.4Hz)，7.43-7.48(4H，m)，7.53(1H，d，J＝15.6Hz)，7.63(1H，dd，J＝8.5 and 1.3Hz)，7.67(1H，d，J＝15.5Hz)，7.77(1H，d，J＝1.9Hz)，7.78(2H，d，J＝2.0Hz)，7.85(1H，d，J＝8.5Hz)，8.34(1H，s)，12.35(1H，brs).IR(Nujol)：1691cm^-1mp: 211.5-212.5 ℃ EXAMPLE 62-1

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (0.27g), N' -carbonyldiimidazole (0.26g), DBU (0.26ml) and 1-pentene-1-sulfonamide (0.26g), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (((E) -pentene-1-sulfonyl) carbamoyl) benzo [ b ] furan (0.095g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.86(3H，t，J＝7.4Hz)，1.39-1.48(2H，m)，2.23(2H，quartet，J＝7.3Hz)，2.41(3H，s)，4.08(2H，s)，6.76(1H，d，J＝15.1Hz)，6.83-6.90(1H，m)，7.17(1H，d，J＝8.4Hz)，7.33(1H，dd，J＝8.3 and 2.2Hz)，7.60(1H，d，J＝8.6Hz)，7.64(1H，d，J＝2.7Hz)，7.80(1H，dd，J＝8.6 and 1.8Hz)，7.96(1H，d，J＝1.7Hz)，12.07(1H，brs).IR(Nujol)：1659cm^-1mp: 158-

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (0.27g), N' -carbonyldiimidazole (0.26g), DBU (0.26ml) and (E) - (2-phenylethene) sulfonamide (0.31g), there was obtained (E) -3- (2, 4-dichlorobenzyl) -2-methyl-5- ((2-phenylethenyl) sulfonylcarbamoyl) benzo [ b ] furan (0.14g) as pale yellow crystals.¹H-NMH(DMSO-d₆，δppm)：2.39(3H，s)，4.07(2H，s)，7.15(1H，d，J＝8.4Hz)，7.31(1H，dd，J＝8.4 and 2.1Hz)，7.40-7.57(6H，m)，7.62(1H，d，J＝2.2Hz)，7.69-7.72(2H，m).7.83(1H，dd，J＝8.6 and 1.8Hz)，7.97(1H，d，J＝1.7Hz).IR(Nujol)：1685cm^-1mp: 184 ℃ and 185 ℃ examples 62-3

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (0.27g), N' -carbonyldiimidazole (0.26g), DBU (0.26ml) and 4-vinylbenzenesulfonamide (0.31g), 3- (2, 4-dichlorobenzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) benzo [ b ] furan (0.23g) was obtained as a pale yellow powder. ¹H-NMR(DMSO-d₆，δppm)：2.39(3H，s)，4.07(2H，s)，5.46(1H，d，J＝11.1Hz)，6.01(1H，d，J＝17.6Hz)，6.82(1H，dd，J＝17.7 and 11.1Hz)，7.16(1H，d，J＝8.4Hz)，7.32(1H，dd，J＝8.3 and 2.2Hz)，7.57(1H，d，J＝8.7Hz)，7.62(1H，d，J＝2.1Hz)，7.70(2H，d，J＝8.4Hz)，7.75(1H，dd，J＝8.6 and 1.8Hz)，7.91-7.94(3H，m)，12.40(1H，brs)IR(Nujol)：1684cm^-1mp: 210 ℃ and 211 ℃ example 63-1

In the same manner as in example 1, from 5-carboxy-3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] furan (0.25g),N, N' -carbonyldiimidazole (0.23g), DBU (0.22ml) and 1-pentanesulfonamide (0.22g) were added to give 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) benzo [ b ] furan (0.20g) as white crystals.¹H-NMR(DMSO-d₆，δppm)：0.77(3H，t，J＝7.3Hz)，1.19-1.35(4H，m)，1.61-1.67(2H，m)，2.45(3H，s)，3.45-3.55(2H，m)，4.14(2H，s)，7.25(1H，d，J＝8.1Hz)，7.36(1H，t，J＝7.3Hz)，7.44(2H，t，J＝7.6Hz)，7.54(1H，dd，J＝8.0and 1.8Hz)，7.61(1H，d，J＝8.7Hz)，7.65(2H，d，J＝7.3Hz)，7.76(1H，d，J＝1.8Hz)，7.83(1H，dd，J＝8.7 and 1.8Hz)，8.05(1H，s)，12.01(1H，brs).IR(Nujol)：1685cm^-1mp: 150 ℃ 151 ℃ example 63-2

According to the same manner as in example 1, from 5-carboxy-3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] furan (0.25g), N' -carbonyldiimidazole (0.23g), DBU (0.22ml) and benzenesulfonamide (0.23g), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] furan (0.18g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：2.43(3H，s)，4.12(2H，s)，7.22(1H，d，J＝8.1Hz)，7.37(1H，t，J＝7.4Hz)，7.45(2H，t，J＝7.6Hz)，7.53(1H，d.J＝8.1Hz)，7.57-7.62(3H，m)，7.63-7.69(3H，m)，7.74-7.77(2H，m)，7.95-8.00(3H，m)，12.45(1H，brs).IR(Nujol)：1703cm^-1mp: 185 ℃ and 186 ℃ example 63-3

According to the same manner as in example 1, from 5-carboxy-3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] furan (0.25g), N' -carbonyldiimidazole (0.23g), DBU (0.22ml) and (E) - (2-phenylethene) sulfonamide (0.27g), white crystalline (E) -3- (2-chloro-4-phenylbenzyl) -2-methyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) benzo [ b ] furan (0.28g) was obtained. ¹H-NMR(DMSO-d₆，δppm)：2.43(3H，s)，4.12(2H，s)，7.20(1H，d，J＝7.8Hz)，7.34-7.58(10H，m)，7.64(2H，d，J＝7.4Hz)，7.69(2H，brs)，7.75(1H，s)，8.04(1H，s).IR(Nujol)：1698cm^-1mp: 218-

According to the same manner as in example 1, from 5-carboxy-3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] furan (0.25g), N' -carbonyldiimidazole (0.23g), DBU (0.22ml) and 4-vinylbenzenesulfonamide (0.27g), 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (4-vinylbenzenesulfonylcarbamoyl) benzo [ b ] furan (0.28g) was obtained as a white powder.¹H-NMR(DMSO-d₆，δppm)：2.43(3H，s)，4.12(2H，s)，5.44(1H，d，J＝11.0Hz)，5.99(1H，d，J＝17.7Hz)，6.78(1H，dd，J＝17.7 and 11.0Hz)，7.22(1H，d，J＝8.2Hz)，7.37(1H，t，J＝7.2Hz)，7.44(2H，t，J＝7.7Hz)，7.54(1H，dd，J＝8.1 and 1.8Hz)，7.59(1H，d，J＝8.7Hz)，7.64-7.69(4H，m)，7.74-7.77(2H，m)，7.93(2H，d，J＝8.4Hz)，8.00(1H，d，J＝1.7Hz)，12.46(1H，brs).IR(Nujol)：1706cm^-1mp: 176 ℃ 178 ℃ example 63-5

According to the same manner as in example 1, from 5-carboxy-3- (2-chloro-4-phenylbenzyl) -2-methylbenzo [ b ] furan (0.22g), N' -carbonyldiimidazole (0.16g), DBU (0.15ml) and 1-pentene-1-sulfonamide (0.27g), 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- (((E) -1-pentene-1-sulfonyl) carbamoyl) benzo [ b ] furan (0.28g) was obtained as a white powder.¹H-NMR(DMSO-d₆，δppm)：0.84(3H，t，J＝7.4Hz)，1.37-1.45(2H，m)，2.18-2.24(2H，m)，2.45(3H，s)，4.14(2H，s)，6.75(1H，d，J＝15.2Hz)，6.82-6.89(1H，m)，7.23(1H，d，J＝8.0Hz)，7.37(1H，t，J＝7.4Hz)，7.44(2H，t，J＝7.6Hz)，7.77(1H，d，J＝1.9Hz).7.81(1H，d，J＝8.6Hz)，8.04(1H，s)，12.07(1H，brs).IR(Nujol)：1688cm^-1mp: example 64-1 at 167 ℃ 166-

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -5-carboxy-2-methylbenzo [ b ] furan (0.21g), N' -carbonyldiimidazole (0.19g), DBU (0.18ml) and 1-pentanesulfonamide (0.18g), 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) benzo [ b ] furan (0.07g) was obtained as white crystals. ¹H-NMR(DMSO-d₆，δppm)：0.81(3H，t，J＝7.3Hz)，1.23-1.29(2H，m)，1.31-1.38(2H，m)，1.63-1.70(2H，m)，2.42(3H，s)，3.49(2H，t，J＝7.8Hz)，4.07(2H，s)，7.12(1H，d，J＝8.4Hz)，7.45(1H，dd，J＝8.3 and 2.1Hz)，7.61(1H，d，J＝8.6Hz)，7.75(1H，d，J＝2.1Hz)，7.82(1H，dd，J＝8.6 and 1.9Hz)，7.99(1H，d，J＝1.7Hz)，11.95(1H，brs).IR(Nujol)：1688cm^-1mp: 133-134.5 ℃ example 64-2

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -5-carboxy-2-methylbenzo [ b ] furan (0.21g), N' -carbonyldiimidazole (0.19g), DBU (0.18ml) and benzenesulfonamide (0.18g), 5- (benzenesulfonylcarbamoyl) -3- (4-bromo-2-chlorophenylmethyl) -2-methylbenzo [ b ] furan (0.21g) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：2.39(3H，s)，4.05(2H，s)，7.09(1H，d，J＝8.3Hz)，7.45(1H，dd，J＝8.3 and 2.0Hz)，7.58(1H，d，J＝8.7Hz)，7.62(2H，t，J＝7.7Hz)，7.68-7.72(1H，m)，7.74(1H，d，J＝2.1Hz)，7.75(1H，dd，J＝8.7 and 1.8Hz)，7.93(1H，d，J＝1.7Hz)，7.96-7.99(2H，m)，12.45(1H，brs).IR(Nujol)：1703cm^-1Mp: 176-

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -5-carboxy-2-methylbenzo [ b ] furan (0.21g), N' -carbonyldiimidazole (0.19g), DBU (0.18ml) and (E) - (2-phenylethene) sulfonamide (0.21g), white crystalline (E) -3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) benzo [ b ] furan (0.13g) was obtained.¹H-NMR(DMSO-d₆，δppm)：2.40(3H，s)，4.05(2H，s)，7.09(1H，d，J＝8.3Hz)，7.42-7.47(5H，m)，7.49(1H，d，J＝15.4Hz)，7.59(1H，d，J＝8.7Hz)，7.64(1H，d，J＝15.5Hz)，7.73(1H，d，J＝2.1Hz)，7.74-7.77(1H，m)，7.82(1H，dd，J＝8.7 and 1.9Hz)，7.99(1H，d，J＝1.8Hz)，12.20(1H，brs).IR(Nujol)：1687cm^-1mp: 214 ℃ 215 ℃ example 65-1

By following the same procedure as in example 1, starting from 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (100mg) and (4-methylbenzene) sulfonamide (76mg) gave 3- (2, 4-dichlorobenzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (84mg) as colorless crystals.¹H-NMR(CDCl₃): 2.42(3H, s), 2.62(3H, s), 5.55(2H, s), 6.70(1H, d, J ═ 8Hz), 7.21(1H, dd, J ═ 8 and 1Hz), 7.35(2H, d, J ═ 8Hz), 7.52(1H, d, J ═ 1Hz), 8.01-8.12(3H, m). M/z 487(M-1) mp: 127 ℃ and 128 ℃ examples 65-2

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (100mg) and (4-vinylbenzene) sulfonamide (82mg), colorless crystals of 3- (2, 4-dichlorobenzyl) -2-methyl-5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (96mg) were obtained.¹H-NMR(CDCl₃): 2.60(3H, s), 5.42(1H, d, J ═ 10Hz), 5.54(2H, s), 5.89(1H, d, J ═ 16Hz), 6.65 to 6.80(2H, m), 7.21(1H, dd, J ═ 8 and 1Hz), 7.50 to 7.59(3H, m), 8.04 to 8.14(4H, m). mass esi (esi): m/z 499(M-1) mp: 194 ℃ and 195 ℃ example 65-3

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (100mg) and (E) - (2-phenylethene) sulfonamide (82mg), colorless crystals of (E) -3- (2, 4-dichlorobenzyl) -2-methyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (96mg) were obtained.¹H-NMR(CDCl₃): 2.61(3H, s), 5.56(2H, s), 6.62(1H, d, J ═ 8Hz), 7.10-7.21(2H, m), 7.37-7.46(2H, m), 7.50-7.58(2H, m), 7.82(1H, d, J ═ 15Hz), 8.11(1H, d, J ═ 8Hz), 8.19(1H, d, J ═ 8Hz), 10.0(1H, s) mass (esi): m/z 499(M-1) mp: 192 ℃ 194 ℃ example 65-4

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (165mg) and 5-chlorothiophene-2-sulfonamide (140mg), 5- [ (5-chlorothien-2-yl) sulfonylcarbamoyl was obtained as a white powderYl ] -3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (150 mg).¹H-NMR(CDCl₃)：2.61(3H，s)，5.55(2H，s)，6.68(1H，d，J＝8Hz)，6.95(1H，d，J＝4Hz)，7.20(1H，dd，J＝8 and 2Hz)，7.52(1H，d，J＝2Hz)，7.76(1H，d，J＝4Hz)，8.11(1H，d，J＝8Hz)，8.15(1H，d，J＝8Hz)，10.05(1H，brs).Mass(ESI)：m/e 513(M-H)^-mp: 206-

According to the same manner as in example 1, from 3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (166mg) and 5-bromothiophene-2-sulfonamide (176mg), 5- [ (5-bromothien-2-yl) sulfonylcarbamoyl ] -3- (2, 4-dichlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (152mg) was obtained as a white powder.¹H-NMR(CDCl₃)：2.64(3H，s)，5.56(2H，s)，6.68(1H，d，J＝8Hz)，7.10(1H，d，J＝4Hz)，7.22(1H，d，J＝8Hz)，7.53(1H，s)，7.74(1H，d，J＝4Hz)，8.11(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz)，10.05(1H，brs).Mass(ESI)：m/e 557，559(M-H)^-mp: 168-

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (100mg) and (E) - (2-phenylethene) sulfonamide (72mg), colorless crystals of (E) -3- (4-bromo-2-chlorophenylmethyl) -2-methyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (77mg) were obtained.¹H-NMR(CDCl₃): 2.61(3H, s), 5.56(2H, s), 6.62(1H, d, J ═ 8Hz), 7.15(1H, d, J ═ 15Hz), 7.33(1H, dd, J ═ 8 and 1Hz), 7.38-7.46(3H, m), 7.50-7.58(2H, m), 7.68(1H, brs), 7.81(1H, d, J ═ 15Hz), 8.11(1H, d, J ═ 8Hz), 8.19(1H, d, J ═ 8Hz), 10.0(1H, brs). mass (esi): m/z 545(M-1) mp: 204-

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (100mg) and (4-vinylbenzene) sulfonamide (72mg), colorless crystals of 3- (4-bromo-2-chlorophenylmethyl) -5-carboxylic acid were obtained4-bromo-2-chlorophenylmethyl) -2-methyl-5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (96 mg).¹H-NMR(CDCl₃): 2.61(3H, s), 5.44(1H, d, J ═ 10Hz), 5.52(2H, s), 5.89(1H, d, J ═ 16Hz), 6.61(1H, d, J ═ 8Hz), 6.75(1H, dd, J ═ 16 and 10Hz), 7.38(1H, d, J ═ 8Hz), 7.54(2H, d, J ═ 8Hz), 7.69(1H, brs), 8.03-8.15(4H, m) · mass (esi): m/z 545(M-1) mp: 208-210 ℃ example 67-1

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (100mg) and (4-vinylbenzene) sulfonamide (73mg), colorless crystals of 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (70mg) were obtained.¹H-NMR(CDCl₃): 2.67(3H, s), 5.42(1H, d, J ═ 10Hz), 5.61(2H, s), 5.85(1H, d, J ═ 16Hz), 6.70(1H, dd, J ═ 16 and 10Hz), 6.89(1H, d, J ═ 8Hz), 7.38-7.52(6H, m), 7.59(2H, d, J ═ 8Hz), 7.73(1H, brs), 8.01-8.12(4H, m). mas (esi): m/z 541(M-1) mp: 178 ℃ and 179 ℃ example 67-2

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine-5-carboxylic acid (100mg) and (E) - (2-phenylethene) sulfonamide (73mg), colorless crystals of (E) -3- (2-chloro-4-phenylbenzyl) -2-methyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [4, 5-b ] pyridine (78mg) were obtained.¹H-NMR(CDCl₃): 2.66(3H, s), 5.61(2H, s), 6.80(1H, d, J ═ 8Hz), 7.12(1H, d, J ═ 15Hz), 7.34-7.60(11H, m), 7.71(1H, d, J ═ 2Hz), 7.79(1H, d, J ═ 15Hz), 8.11(1H, d, J ═ 8Hz), 8.19(1H, d, J ═ 8Hz), 10.6(1H, brs). mass (esi): m/z 541(M-1) mp: 216 ℃ and 218 ℃ examples 67-3

In the same manner as in example 1 and from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [4, 5-b]Pyridine-5-carboxylic acid (100mg) and 5-chlorothiophene-2-sulfonamide (79mg) gave 3- (2-chloro-4-phenylphenylmethyl) -5- [ (5-chloro-5-phenyl) methyl ester as a colorless crystalline substance-chlorothien-2-yl) sulfonylcarbamoyl]-2-methyl-3H-imidazo [4, 5-b]Pyridine (78 mg).¹H-NMR(CDCl₃): 2.69(3H, s), 5.60(2H, s), 6.84-6.91(2H, m), 7.34-7.50(4H, m), 7.52-7.60(2H, m), 7.67-7.74(2H, m), 8.09(1H, d, J ═ 8Hz), 8.13(1H, d, J ═ 8Hz). M/z 555(M-1) mp: 210 ℃ and 212 ℃ examples 67-4

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-methylbenzene) sulfonamide (136mg), 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (221mg) was obtained as colorless crystals.¹H-NMR(CDCl₃): 2.39(3H, s), 2.67(3H, s), 5.62(2H, s), 6.87(1H, d, J ═ 8Hz), 7.27(2H, d, J ═ 8Hz), 7.36-7.50(4H, m), 7.58(2H, d, J ═ 8Hz), 7.72(1H, d, J ═ 2Hz), 7.99(2H, d, J ═ 8Hz), 8.05(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), masss (esi): m/z 529(M-1) mp: 171 ℃ and 173 ℃ examples 67-5

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-bromothiophene-2-sulfonamide (192mg), colorless crystals of 5- [ (5-bromothien-2-yl) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (198mg) were obtained.¹H-NMR(CDCl₃): 2.68(3H, s), 5.61(2H, s), 6.87(1H, d, J ═ 8Hz), 7.03(1H, d, J ═ 5Hz), 7.36-7.50(4H, m), 7.57(2H, d, J ═ 8Hz), 7.65(1H, d, J ═ 5Hz), 7.72(1H, s), 8.09(1H, d, J ═ 8Hz), 8.15(1H, d, J ═ 8Hz), mass (esi): m/z 601(M-1) mp: 205 ℃ 207 ℃ example 67-6

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-ethylbenzene) sulfonamide (147mg), colorless crystals of 3- (2-chloro-4-phenylbenzyl) -5- [ (4-ethylbenzene) sulfonylcarbamoyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (213mg) were obtained.¹H-NMR(CDCl₃): 1.22(3H, t, J ═ 8Hz), 2.63-2.75(5H, m), 5.62(2H, s), 6.88(1H, d, J ═ 8Hz), 7.29(2H, d, J ═ 8Hz), 7.36-7.50(4H, m), 7.60(2H, d, J ═ 8Hz), 7.73(1H, d, J ═ 2Hz), 8.01(2H, d, J ═ 8Hz), 8.07(1H, d, J ═ 8Hz), 8.11(1H, d, J ═ 8Hz). mass (esi): m/z 529(M-1) mp: 205 ℃ 206 ℃ EXAMPLE 68

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (58mg) and benzenesulfonamide (36mg), colorless crystals of 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (53mg) were obtained.¹H-NMR(CDCl₃): 2.66(3H, s), 5.59(2H, s), 6.85(1H, d, J ═ 8Hz), 7.10(1H, t, J ═ 4Hz), 7.32-7.39(2H, m), 7.44-7.52(3H, m), 7.59(2H, d, J ═ 8Hz), 7.72(1H, brs), 8.05-8.14(4H, m). mass (esi): m/z 521(M-1) mp: 225- & 226 ℃ EXAMPLE 69

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (30mg) and benzenesulfonamide (17mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (27mg) was obtained as colorless crystals.¹H-NMR(CDCl₃): 2.66(3H, s), 5.59(2H, s), 6.82(1H, d, J ═ 8Hz), 6.91(1H, d, J ═ 4Hz), 7.12(1H, d, J ═ 4Hz), 7.38(1H, d, J ═ 8Hz), 7.46-7.54(2H, m), 7.59-7.65(2H, m), 8.04-8.19(4H, m) massesi (esi): m/z 555(M-1) mp: 215 ℃ 217 ℃ example 70-1

According to the same manner as in example 1, from 3- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (42mg) and 1-pentanesulfonamide (29mg), 3- (2-chloro-4-ethylbenzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (42mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃)：0.89(3H，t，J＝8Hz)，1.22(3H，d，J＝8Hz)，1.28-1.50(4H，m)，1.81-1.95(2H，m)，2.58-2.68(5H, m), 3.51-3.59(2H, m), 5.55(2H, s), 6.65(1H, d, J ═ 8Hz), 7.02(1H, brd, J ═ 8Hz), 7.31(1H, brs), 8.12(1H, d, J ═ 8Hz), 8.20(1H, d, J ═ 8Hz), 9.81(1H, brs). s esi): m/z 461(M-1) mp: 138-139 ℃ example 70-2

According to the same manner as in example 1, from 3- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (42mg) and benzenesulfonamide (30mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (30mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 1.24(3H, t, J ═ 8Hz), 2.59 to 2.70(5H, m), 5.56(2H, s), 6.68(1H, d, J ═ 8Hz), 7.04(1H, brd, J ═ 8Hz), 7.33(1H, brs), 7.51 to 7.68(3H, m), 8.05(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), 8.19(2H, d, J ═ 8Hz), masss (esi): m/z 467(M-1) mp: 167-

According to the same manner as in example 1, from 3- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (42mg) and (4-methylbenzene) sulfonamide (33mg), 3- (2-chloro-4-ethylbenzyl) -2-methyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (33mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 1.24(3H, t, J ═ 8Hz), 2.41(3H, s), 2.60-2.70(5H, m), 5.56(2H, s), 6.65(1H, d, J ═ 8Hz), 7.04(1H, brd, J ═ 8Hz), 7.30-7.37(3H, m), 8.01-8.10(4H, m), mass (esi): m/z 481(M-1) mp: 190 ℃ 191 ℃ example 70-4

According to the same manner as in example 1, from 3- (2-chloro-4-ethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (42mg) and (E) - (2-phenylethene) sulfonamide (35mg), there was obtained (E) -3- (2-chloro-4-ethylbenzyl) -2-methyl-5- [ (2-phenylvinyl) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (33mg) as pale yellow crystals.¹H-NMR(CDCl₃)：1.23(3H，t，J＝8Hz)，2.57-2.68(5H，m)，5.55(2H，s)，6.61(1H，d，J＝8Hz)，7.02(1H，brd，J＝8Hz)，7.15(1H，d，J＝15Hz)，7.31(1H, brs), 7.36-7.46(3H, m), 7.55(2H, d, J ═ 8Hz), 7.81(1H, d, J ═ 15Hz), 8.09(1H, d, J ═ 8Hz), 8.18(1H, d, J ═ 8Hz) mass (esi): m/z 493(M-1) mp: example 71 at 185 ℃ C

According to the same manner as in example 1, from 3- (2-chloro-4-vinylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (125mg) and benzenesulfonamide (69mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-vinylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (46mg) was obtained as pale yellow crystals.¹H-NMR(CDCl₃): 2.62(3H, s), 5.37(1H, d, J ═ 10Hz), 5.57(2H, s), 5.80(1H, d, J ═ 16Hz), 6.68(1H, dd, J ═ 16 and 10Hz), 6.86(1H, d, J ═ 8Hz), 7.23-7.30(1H, overlaid with H2O), 7.49-7.69(4H, m), 8.05(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), 8.17(2H, d, J ═ 8Hz). mass (esi): m/z 465(M-1) mp: 174 ℃ 175 ℃ example 72

According to the same manner as in example 1, from 3- (2-chloro-4-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (60mg) and benzenesulfonamide (49mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-methylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (50mg) was obtained as a white powder.¹H-NMR(CDCl₃)：2.35(3H，s)，2.61(3H，s)，5.54(2H，s)，6.66(1H，d，J＝8Hz)，7.02(1H，d)，7.31(1H，s)，7.48-7.69(3H，m)，8.00-8.10(2H，m)，8.12-8.21(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 453(M-H)^-mp: 213-215 ℃ EXAMPLE 73

According to the same manner as in example 1, from 3- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (110mg) and benzenesulfonamide (70mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (n-pentyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (81mg) was obtained as a white powder.¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.24-1.38(4H，m)，1.50-1.68(2H，m)2.52-2.64(2H，m)，2.62(3H，s)，5.56(2H，s)，6.64(1H，d，J＝8Hz)，7.02(1H，d，J＝8Hz)，7.31(1H，s)，7.48-7.68(3H，m)，8.01-8.12(2H，m)，8.14-8.22(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 509(M-H)^-mp: 174 ℃ 175 ℃ example 74

According to the same manner as in example 1, from 3- (2-chloro-4-isobutylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (102mg) and benzenesulfonamide (70mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-isobutylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (99mg) was obtained as a white powder.¹H-NMR(CDCl₃)：0.90(6H，d，J＝7Hz)，1.76-1.95(1H，m)，2.46(2H，d，J＝7Hz)，2.61(3H，s)，5.56(2H，s)，6.63(1H，d，J＝8Hz)，6.98(1H，d，J＝8Hz)，7.29(1H，s)，7.49-7.68(3H，m)，8.01-8.12(2H，m)，8.14-8.22(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 495(M-H)^-mp: 183 ℃ 184 ℃ example 75

According to the same manner as in example 1, from 3- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (141mg) and benzenesulfonamide (88mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (cyclohexylmethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (120mg) was obtained as a white powder. ¹H-NMR(CDCl₃)：0.82-1.76(11H，m)，2.46(2H，d，J＝7Hz)，2.61(3H，s)，5.56(2H，s)，6.61(1H，d，J＝8Hz)，6.97(1H，d，J＝8Hz)，7.28(1H，s)，7.49-7.69(3H，m)，8.01-8.12(2H，m)，8.14-8.21(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 535(M-H)^-mp: 170 ℃ 171 ℃ example 76

According to the same manner as in example 1, from (E) -3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (140mg) and benzenesulfonamide (85mg), there was obtained (E) -5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (128mg) as a white powder.¹H-NMR(CDCl₃)：2.66(3H，s)，5.58(2H，s)，6.83(1H，d，J＝8Hz)，7.03(1H，d，J＝16Hz)，7.16(1H，d，J＝16Hz)，7.27-7.66(10H，m)，8.01-8.11(2H，m).8.11-8.30(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 541(M-H)^-mp: example 77 at 262-263 deg.C

According to the same manner as in example 1, from 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (98mg) and benzenesulfonamide (57mg), 5- (benzenesulfonylcarbamoyl) -3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (8mg) was obtained as a white powder.¹H-NMR(CDCl₃)：2.63(3H，s)，5.08(2H，s)，5.52(2H，s)，6.79(1H，d，J＝8Hz)，6.88(1H，dd，J＝8 and 2Hz)，7.12(1H，d，J＝2Hz)，7.30-7.45(5H，m)，7.48-7.66(3H，m)，8.00-8.10(2H，m)，8.12-8.22(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 545(M-H)^-mp: 190 ℃ 191 ℃ example 78

According to the same manner as in example 1, from 3- (2-chloro-4-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (65mg) and benzenesulfonamide (50mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-methoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (51mg) was obtained as a white powder.¹H-NMR(CDCl₃)：2.63(3H，s)，3.81(3H，s)，5.51(2H，s)，6.80(2H，s)，7.02(1H，s)，7.49-7.68(3H，m)，7.99-8.10(2H，m)，8.12-8.22(2H，m)，10.50(1H，brs).Mass(ESI)：m/e 469(M-H)^-mp: example 79 at 151 ℃ and 152 ℃

According to the same manner as in example 1, from 3- (2-chloro-4-isopropylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (61mg) and benzenesulfonamide (45mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-isopropylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (53mg) was obtained as a white powder. ¹H-NMR(CDCl₃)：1.33(6H，d，J＝7Hz)，2.63(3H，s)，4.53(1H，sept，J＝7Hz)，5.50(2H，s)，6.75(2H，s)，7.00(1H，s)，7.48-7.70(3H，m)，8.03(1H，d，J＝8Hz)，8.07(1H，d，J＝8Hz)，8.16(2H，d，J＝8Hz)，10.20(1H，brs).Mass(ESI)：m/e 497(M-H)^-mp: 177-

According to the same manner as in example 1, from 3- (4- (n-butoxy) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (75mg) and benzenesulfonamide (51mg), 5- (benzenesulfonylcarbamoyl) -3- (4- (n-butoxy) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (88mg) was obtained as a white powder.¹H-NMR(CDCl₃)：0.98(3H，t，J＝7Hz)，1.39-1.57(2H，m)，1.69-1.82(2H，m)，2.63(3H，s)，3.97(2H，t，J＝7Hz)，5.51(2H，s)，6.78(2H，s)，7.02(1H，s)，7.49-7.68(3H，m)，7.99-8.10(2H，m)，8.13-8.20(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 511(M-H)^-mp: 181 ℃ and 182 ℃ example 81

According to the same manner as in example 1, from 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (45mg) and benzenesulfonamide (30mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (46mg) was obtained as a white powder.¹H-NMR(CDCl₃)：0.95-1.90(11H，m)，2.62(3H，s)，3.74(2H，d，J＝7Hz)，5.51(2H，s)，6.78(2H，s)，7.01(1H，s)，7.48-7.68(3H，m)，7.99-8.09(2H，m)，8.12-8.21(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 551(M-H)^-mp: example 82 at 125 ℃

According to the same manner as in example 1, from 3- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (103mg) and benzenesulfonamide (56mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((2- (N-methyl-N- (2-pyridyl) amino) ethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (54mg) was obtained as a white powder. ¹H-NMR(CDCl₃)：2.62(3H，s)，3.12(3H，s)，3.98(2H，t，J＝5Hz)，4.19(2H，t，J＝5Hz)，5.51(2H，s)，6.51(1H，d，J＝8Hz)，6.57(1H，dd，J＝8 and 5Hz)，6.78(2H，s)，7.10(1H，s)，7.38-7.67(4H，m)，7.99-8.10(2H，m)，8.12-8.21(3H，m)，10.05(1H，brs).Mass(ESI)：m/e 591(M+H)⁺mp：104-105 ℃ example 83

According to the same manner as in example 1, from 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (131mg) and benzenesulfonamide (92mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (53mg) was obtained as a white powder.¹H-NMR(CDCl₃)：2.49(3H，s)，2.62(3H，s)，5.52(2H，s)，6.74(1H，d，J＝8Hz)，7.10(1H，d，J＝8Hz)，7.33(1H，s)，7.48-7.68(3H，m)，8.00-8.10(2H，m)，8.12-8.20(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 485(M-H)^-mp: 165-

According to the same manner as in example 1, from 3- (2-chloro-4- (methylsulfinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (99mg) and benzenesulfonamide (64mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylsulfinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (90mg) was obtained as a pale yellow powder.¹H-NMR(CDCl₃)：2.63(3H，s)，2.78(3H，s)，5.63(2H，s)，6.82(1H，d，J＝8Hz)，7.43(1H，d，J＝8Hz)，7.50-7.71(3H，m)，7.88(1H，s)，8.05-8.15(2H，m)，8.15-8.22(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 501(M-H)^-mp: 230 ℃ 231 ℃ example 85

According to the same manner as in example 1, from 3- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (100mg) and benzenesulfonamide (62mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylsulfonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (118mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：2.48(3H，s)，3.29(3H，s)，5.93(2H，s)，6.93(1H，d，J＝8Hz)，7.63(2H，t，J＝8Hz)，7.70-7.80(2H，m)，7.90(1H，d，J＝8Hz)，8.03(2H，d，J＝8Hz)，8.13-8.18(2H，m).Mass(ESI)：m/z 517(M-H)^-Example 86

In the same manner as in example 1 and from 3- (4- (benzylamino) -2-chlorophenylmethyl) -2-methyl -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (70mg) and benzenesulfonamide (41mg) to give 5- (benzenesulfonylcarbamoyl) -3- (4- (benzylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (55mg) as pale yellow crystals.¹H-NMR(DMSO-d₆)：2.45(3H，s)，4.23(2H，d，J＝6Hz)，5.62(2H，s)，6.49(1H，dd，J＝2 and 8Hz)，6.61-6.68(3H，m)，7.20-7.32(5H，m)，7.65(2H，t，J＝8Hz)，7.72(1H，t，J＝7Hz)，7.87(1H，dd，J＝1 and 8Hz)，8.03(2H，d，J＝8Hz)，8.07(1H，d，J＝8Hz).Mass(ESI)：m/z 544(M-H)^-Example 87

According to the same manner as in example 1, from 3- (4- (n-butylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (45mg) and benzenesulfonamide (29mg), 5- (benzenesulfonylcarbamoyl) -3- (4- (n-butylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (50mg) was obtained as pale yellow crystals.¹H-NME(DMSO-d₆)：0.89(3H，t，J＝8Hz)，1.30-1.421(2H，m)，1.43-1.55(2H，m)，2.47(3H，s)，2.93(2H，q，J＝7Hz)，5.63(2H，s)，5.97(1H，t，J＝7Hz)，6.45(1H，d，J＝8Hz)，6.63(1H，d，J＝7Hz)，6.67(1H，d，J＝8Hz)，7.65(2H，t，J＝7Hz)，7.73(1H，t，J＝7Hz)，7.87(1H，dd，J＝1 and 8Hz)，8.02(2H，d，J＝8Hz)，8.08(1H，d，J＝8Hz).Mass(ESI)：m/z 510(M-H)^-Example 88

According to the same manner as in example 1, from 3- (2-chloro-4- (N, N-dimethylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (55mg) and benzenesulfonamide (38mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (N, N-dimethylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (60mg) was obtained as white crystals.¹H-NMR(DMS0-d₆)：2.48(3H，s)，2.89(6H，s)，5.68(2H，s)，6.60(1H，dd，J＝2 and 8Hz)，6.74(1H，d，J＝8Hz)，6.77(1H，d，J＝2Hz)，7.64(2H，t，J＝8Hz)，7.73(1H，t，J＝8Hz)，7.86(1H，d，J＝8Hz)，8.03(2H，d，J＝8Hz)，8.08(1H，d，J＝8Hz).Mass(ESI)：m/z 482(M-H)^-Example 89

According to the same manner as in example 1, from 3- (4- (acetylamino) -2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (98mg) and benzenesulfonamide (64mg), 3- (4- (acetylamino) -2-chlorophenylmethyl) -5- (benzenesulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (92mg) was obtained as white crystals. ¹H-NMR(DMSO-d₆)：2.02(3H，s)，2.44(3H，s)，5.73(2H，s)，6.73(1H，d，J＝8Hz)，7.27(1H，d，J＝8Hz)，7.60(2H，t，J＝7Hz)，7.70(1H，t，J＝7Hz)，7.86(1H，d，J＝8Hz)，7.97-8.00(3H，m)，8.10(1H，d，J＝8Hz).Mass(ESI)：m/z 496(M-H)^-Example 90

According to the same manner as in example 1, from 3- (2-chloro-4- (methylsulfonylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (69mg) and benzenesulfonamide (41mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylsulfonylamino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (61mg) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆)：2.47(3H，s)，3.04(3H，s)，5.77(2H，s)，6.78(1H，d，J＝8Hz)，7.10(1H，d，J＝8Hz)，7.36(1H，s)，7.62(2H，t，J＝7Hz)，7.71(1H，t，J＝7Hz)，7.87(1H，d，J＝8Hz)，8.02(2H，d，J＝8Hz)，8.11(1H，d，J＝8Hz).Mass(ESI)：m/z 532(M-H)^-Example 91

According to the same manner as in example 1, from 3- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (240mg) and benzenesulfonamide (163mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (284mg) was obtained as pale brown crystals.¹H-NMR(DMSO-d₆)：2.47(3H，s)，5.93(2H，s)，6.93(1H，d，J＝8Hz)，7.63(2H，t，J＝7Hz)，7.72(1H，t，J＝7Hz)，7.90(1H，d，J＝8Hz)，8.08(1H，dd，J＝2and 8Hz)，8.15(1H，d，J＝8Hz)，8.43(1H，s).Mass(ESI)：m/z 484(M-H)^-Example 92

By the same method as in example 1, from 3- (2-chloro)-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (199mg) and benzenesulfonamide (142mg) to give 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (115mg) as colorless crystals.¹H-NMR(DMSO-d₆): 2.48(3H, s), 5.92(2H, s), 6.91(1H, d, J ═ 8Hz), 7.60-7.69(2H, m), 7.71(1H, d, J ═ 8Hz), 7.79(1H, d, J ═ 8Hz), 7.90(1H, d, J ═ 8Hz), 8.02(2H, d, J ═ 8Hz), 8.10-8.19(2H, m), 9.99(1H, s), 12.25(1H, brs). mass (esi): m/z 467(M-1) mp: 253- & ltwbr/& gtC example 93

By the same method as in example 1, starting from 3- [ 2-chloro-4 [ (thiazolidine-2, 4-diketo-5-ylidene) methyl ] benzyl]-2-methyl-3H-imidazo [4, 5-b]Pyridine-5-carboxylic acid (59mg) and benzenesulfonamide (32mg) were added to give 5- (benzenesulfonamide carbamoyl) -3- [ 2-chloro-4- [ (2, 4-dioxo-1, 3-thiazolidin-5-ylidene) methyl ] -3- [ 2-chloro-4- [ (2, 4-dioxo-1, 3-thiazolidin-5-ylidene)]Benzyl radical]-2-methyl-3H-imidazo [4, 5-b]Pyridine (46mg) was crystallized in pale yellow.¹H-NMR(DMSO-d₆): 2.48(3H, s), 5.89(2H, s), 6.85(1H, d, J ═ 8Hz), 7.45(1H, brd, J ═ 8Hz), 7.60-7.75(3H, m), 7.79(1H, s), 7.86(1H, s), 7.90(1H, d, J ═ 8Hz), 8.00-8.05(2H, m), 8.15(1H, d, J ═ 8Hz), mass (esi): m/z 566(M-1) mp: 271 ℃ and 274 ℃ example 94

According to the same manner as in example 1, from 3- (2-chloro-4-fluorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine-5-carboxylic acid (65mg) and benzenesulfonamide (48mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-fluorobenzyl) -2-methyl-3H-imidazo [4, 5-b ] pyridine (67mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：2.47(3H，s)，5.81(2H，s)，6.85(1H，dt，J＝1 and 8Hz)，7.15(1H，dt，J＝2 and 8Hz)，7.58-7.67(3H，m)，7.73(1H，t，J＝8Hz)，7.89(1H，d，J＝8Hz)，8.03(2H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/z 457(M-H)^-Example 95

According to the same manner as in example 1, from 2-methyl-3- (2, 4, 6-trichlorophenylmethyl) -3H-imidazo [4, 5-b ] pyridine-5-carboxylic acid (70)mg) and benzenesulfonamide (45mg) to give 5- (benzenesulfonylcarbamoyl) -2-methyl-3- (2, 4, 6-trichlorophenylmethyl) -3H-imidazo [4, 5-b ] pyridine (82mg) as white crystals. ¹H-NMR(DMSO-d₆)：2.68(3H，s)，5.85(2H，s)，7.67(2H，t，J＝8Hz)，7.73-7.81(3H，m)，7.84(1H，d，J＝8Hz)，8.04(2H，d，J＝8Hz)，8.10(1H，d，J＝8Hz).Mass(ESI)：m/z 507(M-H)^-Example 96

According to the same manner as in example 1, from 2-methyl-3- (2, 3, 4-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (140mg) and benzenesulfonamide (89mg), 5- (benzenesulfonylcarbamoyl) -2-methyl-3- (2, 3, 4-trichlorophenylmethyl) -3H-imidazo [ 4, 5-b ] pyridine (141mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：2.46(3H，s)，5.82(2H，s)，6.62(1H，d，J＝8Hz)，7.53(1H，d，J＝8Hz)，7.61(1H，t，J＝8Hz)，7.70(1H，t，J＝8Hz)，7.88(1H，d，J＝8Hz)，8.01(2H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/z 507(M-H)^-Example 97

According to the same manner as in example 1, from 3- (2, 4-dichloro-5-fluorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (100mg) and benzenesulfonamide (67mg), 5- (benzenesulfonylcarbamoyl) -3- (2, 4-dichloro-5-fluorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (108mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：2.50(3H，s)，5.80(2H，s)，6.97(1H，d，J＝9Hz)，7.65(2H，t，J＝8Hz)，7.73(1H，t，J＝8Hz)，7.88(1H，d，J＝8Hz)，7.98(1H，d，J＝8Hz)，8.03(2H，d，J＝8Hz)，8.13(1H，d，J＝8Hz).Mass(ESI)：m/z 491(M-H)^-Example 98

According to the same manner as in example 1, from 3- (2-chloro-4-iodobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (70mg) and benzenesulfonamide (39mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-iodobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (58mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：2.47(3H，s)，5.78(2H，s)，6.50(1H，d，J＝8Hz)，7.60-7.67(3H，m)，7.72(1H，t，J＝7Hz)，7.88(1H，d，J＝8Hz)，7.98(1H，s)，8.03(2H，d，J＝8Hz)，8.13(2H，d，J＝8Hz).Mass(ESI)：m/z 565(M-H)^-Example 99

According to the same manner as in example 1, from 3- ((2, 5-dichlorothien-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (55mg) and benzenesulfonamide (38mg), 5- (benzenesulfonylcarbamoyl) -3- ((2, 5-dichlorothien-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (57mg) was obtained as white crystals. ¹H-NMR(DMSO-d₆)：2.57(3H，s)，5.63(2H，s)，6.95(1H，s)，7.65(2H，t，J＝7Hz)，7.73(1H，t，J＝7Hz)，7.88(1H，d，J＝8Hz)，8.05(2H，d，J＝8Hz)，8.10(1H，d，J＝8Hz).Mass(ESI)：m/z 479(M-H)^-Example 100

According to the same manner as in example 1, from 3- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (80mg) and benzenesulfonamide (55mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4, 5- (methylenedioxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (43mg) was obtained as pale yellow crystals.¹H-NMR(DMSO-d₆)：2.49(3H，s)，5.72(2H，s)，6.03(2H，s)，6.42(1H，s)，7.20(1H，s)，7.63(2H，t，J＝7Hz)，7.72(1H，t，J＝7Hz)，7.87(1H，d，J＝8Hz)，8.03(2H，d，J＝8Hz)，8.10(1H，d，J＝8Hz).Mass(ESI)：m/z 483(M-H)^-Example 101

According to the same manner as in example 1, from 3- ((2-chloroquinolin-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (80mg) and benzenesulfonamide (54mg), 5- (benzenesulfonylcarbamoyl) -3- ((2-chloroquinolin-3-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (20mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：2.53(3H，s)，5.92(2H，s)，7.56-7.72(4H，m)，7.78-8.00(8H，m)，8.15(1H，d，J＝8Hz).Mass(ESI)：m/z 490(M-H)^-Example 102-1

According to the same manner as in example 1The process of (1), from 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (90mg) and benzenesulfonamide (57mg), gives 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (90mg) as white crystals.¹H-NMR(DMSO-d₆)：2.48(3H，s)，5.92(2H，s)，6.90(1H，d，J＝8Hz)，7.61-7.67(3H，m)，7.90(1H，d，J＝8Hz)，8.01-8.03(3H，m)，8.17(1H，d，J＝8Hz).Mass(ESI)：m/z 507(M-H)^-Example 102-2

According to the same manner as in example 1, from 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and 1-pentanesulfonamide (98mg), colorless crystals of 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (143mg) were obtained. ¹H-NMR(CDCl₃): 0.88(3H, t, J ═ 8Hz), 1.27-1.52(4H, m), 1.81-1.95(2H, m), 2.62(3H, s), 3.51-3.59(2H, m), 5.63(2H, s), 6.75(1H, d, J ═ 8Hz), 7.45(1H, brd, J ═ 8Hz), 7.79(1H, brs), 8.16(1H, d, J ═ 8Hz), 8.24(1H, d, J ═ 8Hz), 9.75(1H, brs). mass (esi): m/z 501(M-1) mp: 154 ℃ and 155 ℃ example 102-3

According to the same manner as in example 1, from 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and 4- (methylbenzene) sulfonamide (111mg), colorless crystals of 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (176mg) were obtained.¹H-NMR(CDC1₃): 2.41(3H, s), 2.61(3H, s), 5.62(2H, s), 6.77(1H, d, J ═ 8Hz), 7.32(2H, d, J ═ 8Hz), 7.47(1H, brd, J ═ 8Hz), 7.80(1H, brs), 8.02(2H, d, J ═ 8Hz), 8.09(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), mass (esi): m/z 521(M-1) mp: 174 ℃ 175 ℃ example 103

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-ylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (65mg) and benzenesulfonyl groupAmine (42mg) to give 5- (benzenesulfonylcarbamoyl) -3- (1-bromonaphthalen-2-ylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (67mg) as white crystals. ¹H-NMR(DMSO-d₆)：2.45(3H，s)，6.06(2H，s)，6.80(1H，d，J＝8Hz)，7.60-7.80(5H，m)，7.89-7.94(2H，m)，7.99-8.03(3H，m)，8.17(1H，d，J＝8Hz)，8.33(1H，d，J＝8Hz).Mass(ESI)：m/z 533(M-H)^-Example 104-1

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (328mg) and pentanesulfonamide (183mg), 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- (pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (184mg) was obtained as a white powder.¹H-NMR(CDCl₃)：0.84(3H，t，J＝7Hz)，1.20-1.43(4H，m)，1.73-1.88(2H，m)，2.63(3H，s)，2.74(3H，s)，3.43-3.55(2H，m)，5.79(2H，s)，6.78(1H，d，J＝8Hz)，7.52-7.86(4H，m)，8.02(1H，s)，8.38(1H，d，J＝8Hz)，9.85(1H，brs)Mass(ESI)：m/e 541，543(M-H)^-mp: example 104-2 at 211 ℃ of 210-

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (328mg) and benzenesulfonamide (191mg), 5- (benzenesulfonylcarbamoyl) -3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine (278mg) was obtained as a white powder.¹H-NMR(CDCl₃)：2.63(3H，s)，2.67(3H，s).5.80(2H，s)，6.79(1H，d，J＝8Hz)，7.41-7.88(7H，m)，7.90(1H，s)，8.02-8.12(2H，m)，8.41(1H，d，J＝8Hz)，10.05(1H，brs).Mass(ESI)：m/e 547，549(M-H)^-mp: 229 ℃ 230 ℃ example 104-3

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (337mg) and (E) - (2-phenylvinyl) sulfonamide (228mg), there was obtained (E) -3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4 ] as a white powder,5-b ] pyridine (268 mg).¹H-NMR(CDCl₃)：2.62(3H，s)，2.73(3H，s)，5.80(2H，s)，6.73(1H，d，J＝8Hz)，7.09(1H，d，J＝16Hz)，7.32-7.72(8H，m)，7.77(1H，d，J＝16Hz)，7.80-7.87(1H，m)，7.99(1H，s)，8.39(1H，d，J＝8Hz)，10.07(1H，brs).Mass(ESI)：m/e 573，575(M-H)^-mp: example 104-4 at 262-

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (248mg) and (4-methylbenzene) sulfonamide (156mg), 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (190mg) was obtained as a white powder. ¹H-NMR(CDCl₃)：2.38(3H，s)，2.62(3H，s)，2.68(3H，s)，5.81(2H，s)，6.79(1H，d，J＝8Hz)，7.26(2H，d，J＝8Hz)，7.53-7.88(4H，m)，7.90(1H，s)，7.96(2H，d，J＝8Hz)，8.32(1H，d，J＝8Hz)，10.05(1H，brs).Mass(ESI)：m/e 561，563(M-H)^-mp: 227 ℃ 228 ℃ example 104-5

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (250mg) and (4-vinylbenzene) sulfonamide (165mg), 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (186mg) was obtained as a white powder.¹H-NMR(CDCl₃)：2.62(3H，s)，2.68(3H，s)，5.42(1H，d，J＝10Hz)，5.80(2H，s)，5.85(1H，d，J＝17Hz)，6.71(1H，dd，J＝17 and 10Hz)，6.78(1H，d，J＝8Hz)，7.46(2H，d，J＝8Hz)，7.53-7.88(4H，m)，7.90(1H，s)，8.02(2H，d，J＝8Hz)，8.41(1H，d，J＝8Hz)，10.05(1H，brs).Mass(ESI)：m/e 573，575(M-H)^-mp: example 104-6 at 234-

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (249mg) and 5-chlorothiophene-2-sulfonamide (180mg), 3- (1-bromonaphthalen-2-yl) was obtained as a white powder-2-ylmethyl) -2, 7-dimethyl-5- ((5-chlorothien-2 yl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (207 mg).¹H-NMR(CDCl₃)：2.63(3H，s)，2.70(3H，s)，5.80(2H，s)，6.79(1H，d，J＝8Hz)，6.89(1H，d，J＝4Hz)，7.53-7.88(5H，m)，7.95(1H，s)，8.40(1H，d，J＝8Hz)，10.05(1H，brs).Mass(ESI)：m/e 587，589(M-H)^-mp: 213 ℃ 214 ℃ example 105

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and pentanesulfonamide (92mg), colorless crystals of 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- (pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (159mg) were obtained.¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 8Hz), 1.28-1.50(4H, m), 1.80-1.93(2H, m), 2.60(3H, s), 2.73(3H, s), 3.50-3.59(2H, m), 5.50(2H, s), 6.53(1H, d, J ═ 8Hz), 7.31(1H, brd, J ═ 8Hz), 7.66(1H, brs), 8.02(1H, s), 9.80(1H, brs) mass (esi): m/z 527(M-1) mp: 148- & ltwbr/& gt149 ℃ example 106-1

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and (4-methylbenzene) sulfonamide (104mg), colorless crystals of 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (161mg) were obtained.¹H-NMR(CDCl₃): 2.41(3H, s), 2.59(3H, s), 2.68(3H, s), 5.50(2H, s), 6.59(1H, d, J ═ 8Hz), 7.30-7.38(3H, m), 7.68(1H, d, J ═ 2Hz), 7.90(1H, brs), 8.04(2H, d, J ═ 8Hz). M/z 547(M-1) mp: 206- & lt 208 ℃ example 106-2

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and (E) - (2-phenylethene) sulfonamide (111mg), colorless crystals of (E) -3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (162mg)。¹H-NMR(CDCl₃): 2.60(3H, s), 2.72(3H, s), 5.50(2H, s), 6.51(1H, d, J ═ 8Hz), 7.15(1H, d, J ═ 15Hz), 7.31(1H, brd, J ═ 8Hz), 7.39-7.47(3H, m), 7.50-7.59(2H, m), 7.67(1H, brs), 7.81(1H, d, J ═ 15Hz), 8.00(1H, s), 10.01(1H, brs) mass (esi): m/z 559(M-1) mp: 225 ℃ 227 ℃ example 106-3

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-chlorothiophene-2-sulfonamide (150mg), colorless crystals of 3- (4-bromo-2-chlorophenylmethyl) -5- [ (5-chlorothiophen-2-yl) sulfonylcarbamoyl were obtained]-2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine (191 mg).¹H-NMR(CDCl₃): 2.61(3H, s), 2.70(3H, s), 5.50(2H, s), 6.56(1H, d, J ═ 8Hz), 6.95(1H, d, J ═ 4Hz), 7.32(1H, dd, J ═ 8 and 1Hz), 7.67(1H, brs), 7.76(1H, d, J ═ 4Hz), 7.96(1H, s) mass (esi): m/z 573(M-1) mp: 214-215 ℃ example 106-4

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-vinylbenzene) sulfonamide (139mg), colorless crystals of 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (208mg) were obtained.¹H-NMR(CDCl₃): 2.60(3H, s), 2.68(3H, s), 5.43(1H, d, J ═ 10Hz), 5.50(2H, s), 5.88(1H, d, J ═ 16Hz), 6.57(1H, d, J ═ 8Hz), 6.73(1H, dd, J ═ 16 and 10Hz), 7.34(1H, dd, J ═ 8 and 2Hz), 7.55(2H, d, J ═ 8Hz), 7.68(1H, d, J ═ 2Hz), 7.90(1H, s), 8.10(2H, d, J ═ 8Hz). masss (esi): m/z 559(M-1) mp: 204 ℃ 205 ℃ example 106-5

According to the same manner as in example 1, from 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-bromothiophene-2-sulfonamide (184mg), colorless crystals of 3- (4-bromo-2-chlorophenylmethyl) -5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -2, 7-dimethyl-3H-imidazole were obtainedAzolo [ 4, 5-b ] pyridine (238 mg).¹H-NMR(DMSO-d₆): 2.46(3H, s), 2.62(3H, s), 5.74(2H, s), 6.60(1H, d, J ═ 8Hz), 7.39(1H, d, J ═ 5Hz), 7.46(1H, dd, J ═ 8 and 2Hz), 7.70(1H, d, J ═ 5Hz), 7.83(1H, s), 7.87(1H, d, J ═ 2Hz), mp: 210 ℃ and 211 ℃ example 107-1

According to the same manner as in example 1, from 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (135mg) and benzenesulfonamide (88mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine (81mg) was obtained as a pale brown powder.¹H-NMR(DMSO-d₆)：2.46(3H，s)，2.58(3H，s)，5.89(2H，s)，6.88(1H，d，J＝8Hz)，7.55-7.76(4H，m)，7.98(1H，d，J＝8Hz)，8.07(1H，d，J＝8Hz)，8.23(1H，s)，8.43(1H，s).Mass(ESI)：m/e 498(M-H)^-Example 107-2

According to the same manner as in example 1, from 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (4-methylbenzene) sulfonamide (88mg), 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (151mg) was obtained as a yellow powder. ¹H-NMR(DMSO-d₆)：2.37(3H，s)，2.46(3H，s)，2.58(3H，s)，5.89(2H，s)，6.88(1H，d，J＝8Hz)，7.40(2H，d，J＝8Hz)，7.73(1H，s)，7.88(2H，d，J＝8Hz)，8.08(1H，dd，J＝8 and 2Hz)，8.43(1H，d，J＝2Hz).Mass(ESI)：m/e 512(M-H)^-Examples 107 to 3

According to the same manner as in example 1, from 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (E) - (2-phenylethene) sulfonamide (137mg), there was obtained (E) -3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-5- ((2-phenylethenyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (183mg) as a yellow powder.¹H-NMR(DMSO-d₆)：2.46(3H，s)，2.62(3H，s)，5.90(2H，s)，6.84(1H，d，J＝8Hz)，7.38-7.47(3H，m)，7.49(1H，d，J＝15Hz)，7.65(1H，d，J＝15Hz)，7.70-7.80(2H，m)，7.84(1H，s)，8.07(1H，d，J＝8Hz)，8.42(1H，s).Mass(ESI)：m/e 524(M-H)^-Examples 107 to 4

According to the same manner as in example 1, from 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (4-vinylbenzene) sulfonamide (137mg), 3- (2-chloro-4-nitrobenzyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (85mg) was obtained as a yellow powder.¹H-NMR(DMSO-d₆)：2.48(3H，s)，2.60(3H，s)，5.48(1H，d，J＝12Hz)，5.91(2H，s)，6.02(1H，d，J＝18Hz)，6.82(1H，dd，J＝18 and 12Hz)，6.92(1H，d，J＝8Hz)，7.67-7.78(3H，m)，7.97(2H，d，J＝8Hz)，8.09(1H，d，J＝8Hz)，8.44(1H，s).Mass(ESI)：m/e 524(M-H)^-Example 108

According to the same manner as in example 1, from 3- (2-chloro-4-cyanobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (32mg) and benzenesulfonamide (25mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-cyanobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (24mg) was obtained as a pale yellow powder.¹H-NMR(CDCl₃)：2.59(3H，s)，5.63(2H，s)，6.75(1H，d，J＝8Hz)，7.45-7.70(4H，m)，7.81(1H，s)，8.06-8.20(4H，m)，10.05(1H，brs).Mass(ESI)：m/e 464(M-H)^-mp: 242 ℃ and 243 ℃ example 109-1

According to the same manner as in example 1, from 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and (E) - (2-phenylethene) sulfonamide (119mg), colorless crystals of (E) -3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-5- ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (152mg) were obtained. ¹H-NMR(CDCl₃)：2.62(3H，s)，5.64(2H，s)，6.73(1H，d，J＝8Hz)，7.14(1H，d，J＝15Hz)，7.38-7.48(4H，m)，7.50-7，58(2H，m)，7.78-7.85(2H，m)，8.14(1H, d, J ═ 8Hz), 8.21(1H, d, J ═ 8Hz), 9.97(1H, brs) mass (esi): m/z 533(M-1) mp: 140 ℃ and 142 ℃ in example 109-2

According to the same manner as in example 1, from 3- (2-chloro-4-trifluoromethylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and (4-vinylbenzene) sulfonamide (119mg), colorless crystals of 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (41mg) were obtained.¹H-NMR(CDCl₃): 2.62(3H, s), 5.44(1H, d, J ═ 10Hz), 5.63(2H, s), 5.88(1H, d, J ═ 16Hz), 6.68-6.80(2H, m), 7.47(1H, brd, J ═ 8Hz), 7.54(2H, d, J ═ 8Hz), 7.80(1H, s), 8.08-8.16(4H, m) mass (esi): m/z 533(M-1) mp: 157 ℃ 158 ℃ example 109-3

According to the same manner as in example 1, from 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and 5-chlorothiophene-2-sulfonamide (128mg), colorless crystals of 3- (2-chloro-4- (trifluoromethyl) benzyl) -5- ((5-chlorothiophen-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (189mg) were obtained,¹H-NMR(CDCl₃): 2.62(3H, s), 5.63(2H, s), 6.77(1H, d, J ═ 8Hz), 6.95(1H, d, J ═ 4Hz), 7.46(1H, brd, J ═ 8Hz), 7.75(1H, d, J ═ 4Hz), 7.80(1H, brs), 8.14(1H, d, J ═ 8Hz), 8.19(1H, d, J ═ 8Hz), mass (esi): m/z 547(M-1) mp: 170 ℃ 171 ℃ example 109-4

According to the same manner as in example 1, from 3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and 5-bromothiophene-2-sulfonamide (157mg), colorless crystals of 5- ((5-bromothiophene-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (trifluoromethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (203mg) were obtained.¹H-NMR(CDCl₃)：2.62(3H，s)，5.63(2H，s)，6.76(1H，d，J＝8Hz)，7.09(1H，d，J＝4Hz)，7.46(1H，brd，J＝8Hz)，7.71(1H，d，J＝4Hz)，7.79(1H，brs)，8.14(1H，d，J＝8Hz)，8.19(1H，d，J＝8Hz).Mass(ESI): m/z 593(M-1) mp: example 110 at 172-

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-benzo [ b ] thiophene-5-carboxylic acid (90mg) and benzenesulfonamide (54mg), 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methylbenz [ b ] thiophene (65mg) was obtained as white crystals.¹H-NMR(DMSO-d₆)：2.46(3H，s)，4.30(2H，s)，6.78(1H，d，J＝8Hz)，7.35-7.45(4H，m)，7.58-7.70(5H，m)，7.76-7.80(2H，m)，7.97(2H，d，J＝8Hz)，8.03(1H，d，J＝8Hz)，8.18(1H，s).Mass(ESI)：m/z 530(M-H)^-Example 111-1

According to the same manner as in example 1, from 6-carboxy-1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (200mg) and 5-chlorothiophene-2-sulfonamide (157mg), white crystalline 1- (2-chloro-4-phenylbenzyl) -6- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -3-methyl-1H-indazole (39mg) was obtained.¹H-NMR(DMSO-d₆)：2.48(3H，s)，5.70(2H，s)，6.77(1H，d，J＝8Hz)，6.98(1H，d，J＝3Hz)，7.32(1H，d，J＝3Hz)，7.34-7.47(3H，m)，7.52(1H，d，J＝8Hz)，7.64-7.68(3H，m)，7.74-7.77(2H，m)，8.11(1H，s).Mass(ESI)：m/z 554(M-H)^-Example 111-2

According to the same manner as in example 1, from 6-carboxy-1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (200mg) and 5-bromothiophene-2-sulfonamide (193mg), 6- ((5-bromothien-2-yl) sulfonylcarbamoyl) -1- (2-chloro-4-phenylbenzyl) -3-methyl-1H-indazole (197mg) was obtained as white crystals. ¹H-NMR(DMSO-d₆)：2.50(3H，s)，5.70(2H，s)，6.77(1H，d，J＝8Hz)，7.07(1H，d，J＝3Hz)，7.28(1H，d，J＝4Hz)，7.35-7.48(3H，m)，7.52(1H，d，J＝8Hz)，7.63-7.67(3H，m)，7.73-7.77(2H，m)，8.10(1H，s).Mass(ESI)：m/z 600(M-H)^-Example 112

According to the same manner as in example 1, from 3- (1-bromonaphthalen-2-ylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (209mg) and 5-bromothiophene-2-sulfonamide (166 mg)mg) to give 3- (1-bromonaphthalen-2-ylmethyl) -5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine (216mg) as a white powder.¹H-NMR(CDCl₃)：2.63(3H，s)，2.70(3H，s)，5.80(2H，s)，6.78(1H，d，J＝8Hz)，7.03(1H，d，J＝4Hz)，7.53-7.88(5H，m)，7.95(1H，s)，8.40(1H，d，J＝8Hz)，10.05(1H，brs).Mass(ESI)：m/e 631，633，635(1：2：1，M-H)^-mp: 247 ℃ 248 ℃ example 113

After suspending (E) -5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (42mg) in a mixed solvent of chloroform (4ml), 1, 4-dioxane (2ml) and methanol (2m1), platinum oxide (2mg) was added thereto, and the mixture was stirred at room temperature for 6.5 hours in a hydrogen atmosphere at 1 atm. The reaction mixture was filtered, the solvent was distilled off, and the filtrate was purified by silica gel column chromatography (chloroform/methanol-20/1) and crystallized from ethyl acetate/hexane to give 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (18mg) as a white powder.¹H-NMR(CDCl₃)：2.60(3H，s)，2.90(4H，s)，5.56(2H，s)，6.63(1H，d，J＝8Hz)，7.00(1H，d，J＝8Hz)，7.10-7.32(6H，m)，7.49-7.67(3H，m)，8.02-8.12(2H，m)，8.14-8.21(2H，m)，10.05(1H，brs).Mass(ESI)：m/e 543(M-H)^-mp: 180 ℃ 181 ℃ example 114

5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-nitrobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (245mg) was suspended in ethanol (3ml), and reduced iron (141mg) and acetic acid (0.289ml) were added to the suspension and the mixture was refluxed overnight. The reaction mixture was filtered through celite, washed with a mixed solvent of methanol/chloroform (1/4), and then concentrated under reduced pressure. To the concentrated residue were added a saturated aqueous sodium bicarbonate solution, water, and a mixed solvent of methanol/chloroform (1/4), and the aqueous phase was made alkaline. The insoluble matter deposited at this time was filtered through celite, and washed with a mixed solvent of methanol/chloroform (1/9). The filtrate was separated, dried over anhydrous magnesium sulfate was added to the organic layer, and filtered. Concentrating the filtrate under reduced pressure to obtain a light brown powdery crude product . The crude product (100mg) was recrystallized from N, N-dimethylformamide-water to give 3- (4-amino-2-chlorophenylmethyl) -5- (benzenesulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (75mg) as brown crystals.¹H-NMR(DMSO-d₆)：2.50(3H，s)，5.62(2H，s)，6.45(1H，d，J＝8Hz)，6.62(1H，d，J＝8Hz)，6.67(1H，s)，7.63(2H，t，J＝7Hz)，7.72(1H，t，J＝7Hz)，7.87(1H，d，J＝8Hz)，8.04(2H，d，J＝8Hz)，8.08(1H，d，J＝8Hz).Mass(ESI)：m/z 454(M-H)^-Example 115

From 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (170mg), colorless crystals of 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (hydroxymethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (80mg) were obtained.¹H-NMR(CDCl₃-CD₃OD): 2.64(3H, s), 4.68(2H, s), 5.59(2H, s), 6.80(1H, d, J ═ 8Hz), 7.22(1H, brd, J ═ 8Hz), 8.05(1H, d, J ═ 8Hz), 8.09(1H, d, J ═ 8Hz), 8.13-8.19(2H, m), mass (esi): m/z 469(M-1) mp: example 116 at 198-

To a suspension of 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-formylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (95mg, 0.20mmol) in t-butanol (2ml) and water (0.5ml) at room temperature were added 2-methyl-2-butene (63mg, 0.90mmol) and sodium dihydrogen phosphate (32mg, 0.20 mmol). Sodium hypochlorite (63mg, 0.56mmol) was added to the suspension, and the mixture was stirred at room temperature. After 1 hour, additional 2-methyl-2-butene (63mg, 0.90mmol) and sodium dihydrogen phosphate (32mg, 0.20mmol) were added. After 2 hours 1, 4-dioxane (2ml) was added and the mixture was heated at 60 ℃. When the solution became a transparent solution, the solution was stirred at room temperature for 1 hour. Water was added to the reaction solution, and the pH was adjusted to 4 with 1N hydrochloric acid. After stirring for 30 minutes under ice-water bath conditions, it was collected by filtration to give a colorless powder (97 mg). This was suspended in acetone, heated, and then stirred at room temperature for 30 minutes to give 5- (benzenesulfonylcarbamoyl) -3- (4-carboxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (70mg) as colorless crystals. ¹H-NMR(DMSO-d₆)：2.48(3H, s), 5.90(2H, s), 6.82(1H, d, J ═ 8Hz), 7.60-7.68(2H, m), 7.71(1H, d, J ═ 8Hz), 7.80(1H, d, J ═ 8Hz), 8.00-8.08(3H, m), 8.17(1H, d, J ═ 8Hz). M/z 483(M-1) mp: example 117 at 155-

5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((methanesulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (58mg) was obtained from 5- (benzenesulfonylcarbamoyl) -3- [ 2-chloro-4- (hydroxymethyl) benzyl ] -2-methyl-3H-imidazo [ 4, 5-b ] pyridine according to the same procedure as in step 1 of preparation 14. The reaction mixture was used in the following reaction without purification. Example 118

To a solution of phenol (12mg, 0.13mmol) in N, N-dimethylformamide (0.5ml) was added sodium hydride (60% in mineral oil, 5.2mg) under ice-bath conditions. After 30 minutes, a solution of 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((methylsulfonyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (68mg, 0.12mmol) in N, N-dimethylformamide (1ml) was added dropwise, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was cooled with ice, water was added thereto, and 1N hydrochloric acid was added dropwise to adjust the pH to 4. After the product was extracted with ethyl acetate, it was washed with water 3 times, dried over anhydrous magnesium sulfate, and the filtrate was concentrated. The residue was subjected to silica gel thin layer chromatography, developed with chloroform/methanol 20/1, and then crystallized from ethyl acetate to give 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (30mg) as colorless crystals. ¹H-NMR(CDCl₃): 2.62(3H, s), 5.05(2H, s), 5.59(2H, s), 6.74(1H, d, J ═ 8Hz), 6.91-7.01(3H, m), 7.23-7.33(3H, m), 7.49-7.67(4H, m), 8.06(1H, d, J ═ 8Hz), 8.10(1H, d, J ═ 8Hz), 8.15-8.21(2H, m), mass (esi): m/z 545(M-1) mp: 203-

To a solution of 5- (benzenesulfonylcarbamoyl) -3- (4-carboxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (25mg, 0.052mmol) in N, N-dimethylformamide (0.3ml) at room temperature were added ethanol (4mg, 0.088mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochlorideSalt (12mg, 0.062mmol), 1-hydroxybenzotriazole (10mg, 0.075 mmol). After 3 hours, ethyl acetate and water were added to the reaction mixture, and the mixture was adjusted to pH4 with 1N hydrochloric acid. The organic layer was washed with water 4 times, dried over anhydrous magnesium sulfate, and the filtrate was concentrated. The residue was subjected to silica gel thin layer chromatography, developed with chloroform/methanol 10/1, and then crystallized from ethyl acetate to give 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (18mg) as colorless crystals.¹H-NMR(CDCl₃): 1.40(3H, t, J ═ 8Hz), 2.60(3H, s), 4.40(2H, q, J ═ 8Hz), 5.63(2H, s), 6.72(1H, d, J ═ 8Hz), 7.50-7.59(2H, m), 7.62(1H, d, J ═ 8Hz), 7.86(1H, d, J ═ 8Hz), 8.09(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), 8.15-8.20(3H, m). mass (esi): m/z 511(M-1) mp: example 120 at 196 ℃ and 197 ℃

From 5- (benzenesulfonylcarbamoyl) -3- (4-carboxy-2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (29mg) and a methylamine/tetrahydrofuran solution (2M, 0.05ml), colorless crystals of 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4- (methylcarbamoyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (18mg) were obtained.¹H-NMR(CDCl₃-CD₃OD): 2.67(3H, s), 3.99(3H, s), 5.60(2H, s), 6.99(1H, d, J ═ 8Hz), 7.50-7.69(4H, m), 7.96(1H, brs), 8.05-8.15(4H, m) mass (esi): m/z 496(M-1) mp: 257 ℃ C example 1215- (benzenesulfonylcarbamoyl) -3- (4-bromo-2-chlorobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine

According to the same manner as in preparation 4, step 7, from 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and benzenesulfonamide (96mg), the desired product (139mg) was obtained as colorless crystals.¹H-NMR(CDCl₃): 2.60(3H, s), 2.68(3H, s), 5.51(2H, s), 6.59(1H, d, J ═ 8Hz), 7.35(1H, dd, J ═ 8, 2Hz), 7.51-7.69(4H, m), 7.91(1H, brs), 8.17(2H, d, J ═ 8Hz). M/z 533(M-1) mp 231-

According to the combination of the ingredientsThe same procedures as in example 1 were repeated except for using 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-methylbenzene) sulfonamide (126mg) to give 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (221mg) as a white crystal. ¹H-NMR(CDCl₃)：2.36(3H，s)，2.64(3H，s)，5.58(2H，s)，6.92(1H，d，J＝8Hz)，7.03(1H，d，J＝16Hz)，7.15(1H，d，J＝19Hz)，7.25-7.38(6H，m)，7.50(2H，d，J＝8Hz)，7.63(1H，s)，8.00-8.09(4H，m)Mass(ESI)：m/z 555(M-H)^-Example 123

According to the same manner as in example 1, from 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-vinylbenzene) sulfonamide (135mg), 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (229mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.65(3H，s)，5.37(1H，d，J＝9Hz)，5.57(2H，s)，5.79(1H，d，J＝16Hz)，6.68(1H，dd，J＝9.17Hz)，6.84(1H，d，J＝8Hz)，7.02-7.53(8H，m)，7.63(1H，s)，8.05-8.08(4H，m)Mass(ESI)：m/z 567(M-H)^-Example 124

According to the same manner as in example 1, from 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (E) - (2-phenylvinyl) sulfonamide (135mg), 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (227mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.66(3H，s)，5.58(2H，s)，6，77(1H，d，J＝8Hz)，6.98-7.17(3H，m)，7.29-7.53(11H，m)，7.63(1H，s)，7.77(1H，d，J＝16Hz)，8.10(1H，d，J＝8Hz)，8.15(1H，d，J＝8Hz)Mass(ESI)：m/z 567(M-H)^-Example 125

By the same method as in example 1, from 3- (2-chloro)-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-chlorothiophene-2-sulfonamide (145mg) to give 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -5- ((5-chlorothiophene-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (227mg) as a white crystal. ¹H-NMR(CDCl₃)：2.66(3H，s)，5.57(2H，s)，6.82(1H，d，J＝8Hz)，6.99(1H，d，J＝3Hz)，7.02(1H，d，J＝16Hz)，7.13(1H，d，J＝16Hz)，7.29-7.39(4H，m)，7.50(1H，d，J＝7Hz)，7.63(1H，s)，7.75(1H，d，J＝3Hz)，8.09(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz)Mass(ESI)：m/z 581(M-H)^-Example 126

According to the same manner as in example 1, from 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-bromothiophene-2-sulfonamide (178mg), 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (E) - (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (226mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.68(3H，s)，5.57(2H，s)，6.82(1H，d，J＝8Hz)，7.00-7.16(3H，m)，7.28-7.38(4H，m)，7.51(2H，d，J＝8Hz)，7.63(1H，s)，7.70(1H，d，J＝3Hz)，8.08(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz)Mass(ESI)：m/z 627(M-H)^-Example 127

According to the same manner as in example 1, from 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 1-pentanesulfonamide (11mg), 3- (2-chloro-4- (E) - (2-phenylvinyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (202mg) was obtained as white crystals.¹H-NMR(CDCl₃)：8.03(3H，t，J＝7Hz)，1.22-1.43(4H，m)，1.80-1.92(2H，m)，2.67(3H，s)，3.53(2H，t，J＝8Hz)，5.58(2H，s)，6.77(1H，d，J＝8Hz)，6.99(1H，d，J＝16Hz)，7.13(1H，d，J＝17Hz)，7.29-7.36(4H，m)，7.49(2H，d，J＝8Hz)，7.63(1H，s)，8.13(1H，d，J＝8Hz)，8.20(1H，d，J＝8Hz)Mass(ESI)：m/z 537(M+H)⁺Example 128

According to the same manner as in example 1, from 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-methylbenzene) sulfonamide (127mg), 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (193mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.42(3H，s)，2.02(3H，s)，2.86(4H，s)，5.56(2H，s)，6.62(1H，d，J＝8Hz)，7.00(1H，d，J＝8Hz)，7.13-7.33(8H，m)，8.02-8.09(4H，m)Mass(ESI)：m/z 557(M-H)^-Example 129

According to the same manner as in example 1, from 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-vinylbenzene) sulfonamide (226mg), 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (147mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.61(3H，s)，2.91(4H，s)，5.43(1H，d，J＝10Hz)，5.88(1H，d，J＝16Hz)，6.64(1H，d，J＝8Hz)，6.74(1H，dd，J＝9.16Hz)，7.00(1H，d，J＝8Hz)，7.16-7.33(6H，m)，7.64(2H，d，J＝8Hz)，8.04-8.14(4H，m)Mass(ESI)：m/z 569(M-H)^-Example 130

According to the same manner as in example 1, from 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (E) - (2-phenylethyl) sulfonamide (226mg), 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-5- (E) - ((2-phenylethyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (242mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.61(3H，s)，2.91(4H，s)，5.57(2H，s)，6.62(1H，d，J＝8Hz)，7.00(1H，d，J＝8Hz)，7.14-7.32(7H，m)，7.42-7.45(3H，m)，7.53(2H，d，J＝8Hz)，7.83(1H，d，J＝15Hz)，8.08(1H，d，J＝8Hz)，8.17(1H，d，J＝8Hz)Mass(ESI)：m/z 569(M-H)^-Example 131

According to the same manner as in example 1, from 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-chlorothiophene-2-sulfonamide (243mg), 3- (2-chloro-4- (2-phenylethyl) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (199mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.63(3H，s)，2.92(3H，s)，5.56(2H，s)，6.64(1H，d，J＝8Hz)，6.96(1H，d，J＝3Hz)，7.01(1H，d，J＝8Hz)，7.16-7.32(6H，m)，7.78(1H，d，J＝3Hz)，8.08(1H，d，J＝8Hz)，8.14(1H，d，J＝8Hz)Mass(ESI)：m/z 583(M-H)^-Example 132

According to the same manner as in example 1, from 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-bromothiophene-2-sulfonamide (298mg), 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (263mg) was obtained as white crystals. ¹H-NMR(CDCl₃)：2.62(3H，s)，2.90(4H，s)，5.56(2H，s)，6.65(1H，d，J＝8Hz)，7.01(1H，d，J＝8Hz)，7.08(1H，d，J＝3Hz)，7.12-7.30(6H，m)，7.74(1H，d，J＝4Hz)，8.07(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz)Mass(ESI)：m/z 629(M-H)^-Example 133

According to the same manner as in example 1, from 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 1-pentanesulfonamide (186mg), 3- (2-chloro-4- (2-phenylethyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (166mg) was obtained as white crystals.¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.28-1.47(4H，m)，1.83-1.94(2H，m)，2.62(3H，s)，2.90(4H，s)，3.56(2H，t，J＝8Hz)，5.56(2H，s)，6.63(1H，d，J＝8Hz)，6.97(1H，d，J＝8Hz)，7.13-7.80(6H，m)，8.13(1H，d，J＝8Hz)，8.20(1H，d，J＝8Hz)Mass(ESI)：m/z 537(M-H)^-Example 134

According to the same manner as in example 1, from 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (230mg) and (4-methylbenzene) sulfonamide (145mg), 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (259mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.41(3H，s)，2.64(3H，s)，5.06(2H，s)，5.52(2H，s)，6.78-6.88(2H，m)，7.12(1H，s)，7.29-7.43(7H，m)，8.03-8.07(4H，m)Mass(ESI)：m/z 559(M-H)^-Example 135

According to the same manner as in example 1, from 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-vinylbenzene) sulfonamide (135mg), 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (214mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.63(3H，s)，5.07(2H，s)，5.42(1H，d，J＝9Hz)，5.51(2H，s)，5.86(1H，d，J＝17Hz)，6.67-6.90(3H，m)，7.12(1H，d，J＝2Hz)，7.32-7.43(5H，m)，7.52(2H，d，J＝8Hz)，8.02-8.13(4H，m)Mass(ESI)：m/z 571(M-H)^-Example 136

According to the same manner as in example 1, from 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (E) - (2-phenylethene) sulfonamide (135mg), 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (212mg) was obtained as white crystals. ¹H-NMR(CDCl₃)：2.13(3H，s)，5.06(2H，s)，5.53(2H，s)，6.73(1N，d，J＝8Hz)，6.84(1H，dd，J＝2.8Hz)，7.10-7.18(2H，m)，7.32-7.43(8H，m)，7.50-7.53(2H，m)，7.82(1H，d，J＝15Hz)，8.07(1H，d，J＝8Hz)，8.15(1H，d，J＝8Hz)Mass(ESI)：m/z 571(M-H)^-Example 137

The same procedure was followed as in example 1 using 3- (4-benzyl)Oxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-chlorothiophene-2-sulfonamide (145mg) were added to give 3- (4-benzyloxy-2-chlorophenylmethyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (178mg) as a white crystal.¹H-NMR(CDCl₃)：2.67(3H，s)，5.06(2H，s)，5.51(2H，s)，6.78(1H，d，J＝8Hz)，6.85(1H，dd，J＝2.8Hz)，6.92(1H，d，J＝3Hz)，7.12(1H，d，J＝2Hz)，7.32-7.42(5H，m)，7.78(1H，d，J＝7Hz)，8.06(1H，d，J＝8Hz)，8.10(1H，d，J＝8Hz)Mass(ESI)：m/z 585(M-H)^-Example 138

According to the same manner as in example 1, from 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-bromothiophene-2-sulfonamide (178mg), 3- (4-benzyloxy-2-chlorophenylmethyl) -5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (227mg) was obtained as white crystals.¹H-NMR(CDCl₃)：2.63(3H，s)，5.05(2H，s)，5.52(2H，s)，6.80(1H，d，J＝5Hz)，6.84(1H，dd，J＝2.8Hz)，7.07(1H，d，J＝7Hz)，7.10(1H，d，J＝3Hz)，7.32-7.42(5H，m)，7.72(1H，d，J＝3Hz)，8.07(1H，d，J＝8Hz)，8.12(1H，d，J＝8Hz)Mass(ESI)：m/z 630(M-H)^-Example 139

According to the same manner as in example 1, from 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 1-pentanesulfonamide (111mg), 3- (4-benzyloxy-2-chlorophenylmethyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (184mg) was obtained as white crystals.¹H-NMR(CDCl₃)：0.87(3H，t，J＝8Hz)，1.30-1.48(4H，m)，1.83-1.93(2H，m)，2.64(3H，s)，3.53(2H，t，J＝8Hz)，5.04(2H，s)，5.51(2H，s)，6.74(1H，d，J＝8Hz)，6.82(1H，dd，J＝2.8Hz)，7.10(1H，d，J＝8Hz)，7.30-7.40(5H，m)，8.10(1H，d，J＝8Hz)，8.17(1H，d，J＝8Hz)Mass(ESI)：m/z 539(M-H)^-Example 140

According to the same manner as in example 1, from 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-methylbenzene) sulfonamide (124mg), 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (211mg) was obtained as white crystals. ¹H-NMR(CDCl₃)：0.97-1.36(5H，m)，1.67-1.87(6H，m)，2.41(3H，s)，2.63(3H，s)，3.74(2H，d，J＝7Hz)，5.51(2H，s)，6.77(2H，s)，7.01(1H，s)，7.32(2H，d，J＝8Hz)，8.02-8.07(4H，m)Mass(ESI)：m/z 565(M-H)^-Example 141

According to the same manner as in example 1, from 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-vinylbenzene) sulfonamide (133mg), 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (203mg) was obtained as white crystals.¹H-NMR(CDCl₃)：0.98-1.38(5H，m)，1.68-1.88(6H，m)，2.64(3H，s)，3.75(2H，d，J＝7Hz)，5.43(1H，d，J＝11Hz)，5.50(2H，s)，5.87(1H，d，J＝16Hz)，6.69-6.78(3H，m)，7.00(1H，s)，7.53(2H，d，J＝8Hz)，8.00-8.12(4H，m)Mass(ESI)：m/z 577(M-H)^-Example 142

According to the same manner as in example 1, from 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (E) - (2-phenylethene) sulfonamide (133mg), 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-5- (E) - ((2-phenylethenyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (193mg) was obtained as white crystals.¹H-NMR(CDCl₃)：0.96-1.36(5H，m)，1.68-1.84(6H，m)，2.64(3H，s)，3.72(2H，d，J＝7Hz)，5.51(2H，s)，6.69-6.74(2H，m)，7.00(1H，d，J＝2Hz)，7.14(1H，d，J＝15Hz)，7.36-7.46(3H，m)，7.52-7.56(2H，m)，7.81(1H，d，J＝16Hz)，8.08(1H，d，J＝8Hz)，8.13(1H，d，J＝8Hz)Mass(ESI)：m/z 577(M-H)^-Example 143

According to the same manner as in example 1, from 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-chlorothiophene-2-sulfonamide (143mg), 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (155mg) was obtained as white crystals. ¹H-NMR(CDCl₃)：0.97-1.36(5H，m)，1.37-1.87(6H，m)，2.65(3H，s)，3.73(2H，d，J＝7Hz)，5.50(2H，s)，6.73-6.82(2H，m)，6.94(1H，d，J＝2Hz)，7.00(1H，s)，7.76(1H，d，J＝3Hz)，8.06(1H，d，J＝8Hz)，8.10(1H，d，J＝8Hz)Mass(ESI)：m/z 591(M-H)^-Example 144

According to the same manner as in example 1, from 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-bromothiophene-2-sulfonamide (175mg), 5- ((5-bromothiophene-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (178mg) was obtained as white crystals.¹H-NMR(CDCl₃)：0.97-1.36(5H，m)，1.68-1.87(6H，m)，2.64(3H，s)，3.73(2H，d，J＝7Hz)，5.50(2H，s)，6.72-6.80(2H，m)，7.00(1H，s)，7.08(1H，d，J＝3Hz)，7.72(1H，d，J＝3Hz)，8.05(1H，d，J＝8Hz)，8.11(1H，d，J＝8Hz)Mass(ESI)：m/z 537(M-H)^-Example 145

According to the same manner as in example 1, from 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-3H imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 1-pentanesulfonamide (110mg), 3- (2-chloro-4- ((cyclohexylmethyl) oxy) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (178mg) was obtained as white crystals.¹H-NMR(CDCl₃)：0.88(3H，t，J＝8Hz)，0.96-1.48(9H，m)，1.68-1.92(8H，m)，2.64(3H，s)，3.53(2H，t，J＝8Hz)，3.72(2H，d，J＝7Hz)，5.46(2H，s)，6.70-6.76(2H，m)，6.78(1H，s)，8.09(1H，d，J＝8Hz)，8.16(1H，d，J＝8Hz)Mass(ESI)：m/z 545(M-H)^-Example 146

According to the same manner as in example 1, from 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg), colorless crystals of 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (181mg) were obtained.¹H-NMR(CDCl₃): 2.41(3H, s), 2.50(3H, s), 2.63(3H, s), 5.52(2H, s), 6.73(1H, d, J ═ 8Hz), 7.09(1H, d, J ═ 8Hz), 7.30-7.37(3H, m), 8.00-8.07(4H, m). mass (esi): m/z 499(M-1) mp 180-

According to the same manner as in example 1, from 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg), colorless crystals of 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (174mg) were obtained.¹H-NMR(CDCl₃): 2.50(3H, s), 2.64(3H, s), 5.44(1H, d, J ═ 11Hz), 5.53(2H, s), 5.88(1H, d, J ═ 18Hz), 6.57(1H, d, J ═ 8Hz), 6.71(2H, dd, J ═ 18.11Hz), 7.08(1H, dd, J ═ 8.2Hz), 7.32(1H, d, J ═ 2Hz), 7.54(2H, d, J ═ 8Hz), 8.00-8.14(4H, m). mass (esi): m/z 513(M +1). mp 197-198 ℃ EXAMPLE 148

The same procedures used in example 1 were repeated except for using 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) to give 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (174mg) as colorless crystals.¹H-NMR(CDCl₃): 2.48(3H, s), 2.63(3H, s), 5.53(2H, s), 6.67(1H, d, J ═ 8Hz), 7.06(1H, dd, J ═ 8.1Hz), 7.14(1H, d, J ═ 15Hz), 7.23-7.33(1H, overlappedwith H2O), 7.36-7.47(3H, m), 7.50-7.59(2H, m), 7.81(1H, d, J ═ 15Hz), 8.09(1H, d, J ═ 8Hz), 8.17(1H, d, J ═ 8Hz), 10.01(1H, brs) · mass: m/z 513(M +1). mp 175-

According to the same manner as in example 1, from 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg), colorless crystals of 3- (2-chloro-4- (methylthio) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (186mg) were obtained.¹H-NMR(CDCl₃): 2.40(3H, s), 2.65(3H, s), 5.53(2H, s), 6.73(1H, d, J ═ 8Hz), 6.95(1H, d, J ═ 5Hz), 7.08(1H, dd, J ═ 8.2Hz), 7.31(1H, d, J ═ 2Hz), 7.77(1H, d, J ═ 5Hz), 7.70(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz), mass (esi): m/z 528(M +1). mp 170-171 ℃ example 150

According to the same manner as in example 1, from 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg), colorless crystals of 3- (2-chloro-4- (methylthio) benzyl) -5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (211mg) were obtained.¹H-NMR(CDCl₃): 2.49(3H, s), 2.65(3H, s), 5.52(2H, s), 6.73(1H, d, J ═ 8Hz), 7.02-7.13(2H, m), 7.31(1H, brs), 7.72(1H, d, J ═ 5Hz), 8.08(1H, d, J ═ 8Hz), 8.12(1H, d, J ═ 8Hz). mass (esi): m/z 572(M +1). mp 169- & 170 ℃ example 151

The same procedures used in example 1 were repeated except for using 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) to give 3- (2-chloro-4- (methylthio) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (169mg) as colorless crystals.¹H-NMR(CDCl₃): 0.90(3H, t, J ═ 8Hz), 1.26-1.49(4H, m), 1.81-1.95(2H, m), 2.47(3H, s), 2.64(3H, s), 3.50-3.60(2H, m), 5.52(2H, s), 6.70(1H, d, J ═ 8Hz), 7.05(1H, dd, J ═ 8.1Hz), 7.30(1H, d, J ═ 1Hz), 8.12(1H, d, J ═ 8Hz), 8.19(1H, d, J ═ 8Hz), 9.81(1H, brs). masss (esi): m/z 481(M +1). mp 184-185 ℃ example 152

By the same method as in example 1, from 3- (2-chloro-4- (ethoxycarbonyl)Benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (150mg) and (4-methylbenzene) sulfonamide (103mg) gave 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (173mg) as white crystals.¹H-NMR(CDCl₃)：1.40(3H，t，J＝7Hz)，2.42(3H，s)，2.59(3H，s)，4.39(2H，q，J＝7Hz)，5.63(2H，s)，6.70(1H，d，J＝8Hz)，7.27-7.33(2H，m)，7.83(1H，d，J＝8Hz)，8.00-8.07(5H，m)Mass(ESI)：m/z 525(M-H)^-Example 153

According to the same manner as in example 1, from 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-vinylbenzene) sulfonamide (147mg), 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (212mg) was obtained as white crystals. ¹H-NMR(CDCl₃)：1.40(3H，t，J＝7Hz)，2.59(3H，s)，4.40(2H，q，J＝7Hz)，5.43(1H，d，J＝9Hz)，5.64(2H，s)，5.88(1H，d，J＝16Hz)，6.68-6.77(2H，m)，7.52(1H，d，J＝8Hz)，7.83(1H，dd，J＝2.8Hz)，8.05-8.16(5H，m)Mass(ESI)：m/z 537(M-H)^-Example 154

According to the same manner as in example 1, from 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (E) - (2-phenylethene) sulfonamide (147mg), 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-5- (E) - ((2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (237mg) was obtained as white crystals.¹H-NMR(CDCl₃)：11.38(3H，t，J＝7Hz)，2.60(3H，s)，4.37(2H，q，J＝7Hz)，5.65(2H，s)，6.65(1H，d，J＝8Hz)，7.14(1H，d，J＝15Hz)，7.36-7.53(5H，m)，7.77-7.85(2H，m)，8.12-8.20(3H，m)Mass(ESI)：m/z 537(M-H)^-Example 155

By a method similar to example 1, from 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-chlorothiophene-2-sulfonamide (159mg) to give 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine as a white crystal (210 mg).¹H-NMR(CDCl₃)：1.39(3H，t，J＝7Hz)，2.60(3H，s)，4.38(2H，q，J＝7Hz)，5.62(2H，s)，6.70(1H，d，J＝8Hz)，6.93(1H，d，J＝3Hz)，7.26(1H，s)，7.73(1H，d，J＝4Hz)，7.83(1H，dd，J＝2.8Hz)，8.11-8.17(3H，m)Mass(ESI)：m/z 551(M-H)^-Example 156

According to the same manner as in example 1, from 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-bromothiophene-2-sulfonamide (194mg), 5- ((5-bromothiophene-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (229mg) was obtained as white crystals. ¹H-NMR(CDCl₃)：1.19(3H，t，J＝7Hz)，2.62(3H，s)，4.38(2H，q，J＝8Hz)，5.63(2H，s)，6.71(1H，d，J＝8Hz)，7.07(1H，d，J＝4Hz)，7.71(1H，d，J＝3Hz)，7.83(1H，dd，J＝2.8Hz)，8.09-8.15(3H，m).Mass(ESI)：m/z 597(M-H)^-Example 157

According to the same manner as in example 1, from 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 1-pentanesulfonamide (121mg), 3- (2-chloro-4- (ethoxycarbonyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (197mg) was obtained as white crystals.¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.27-1.47(7H，m)，1.82-1.92(2H，m)，2.60(3H，s)，3.53(2H，t，J＝8Hz)，4.38(2H，q，J＝7Hz)，5.62(2H，s)，6.67(1H，d，J＝8Hz)，7.83(1H，dd，J＝2.8Hz)，8.14-8.24(3H，m)Mass(ESI)：m/z 505(M-H)^-Example 158

According to the same manner as in example 1, from 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-methylbenzene) sulfonic acidAmide (127mg) to give 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H imidazo [ 4, 5-b ] pyridine as pale yellow crystals (182 mg).¹H-NMR(300MHz，DMSO-d₆) δ: 2.38(s, 3H), 2.48(s, 3H), 5.12(s, 2H), 5.83(s, 3H), 6.76(d.J ═ 8Hz, 1H), 6.90-7.04(m, 3H), 7.24-7.38(m.3h), 7.42(d, J ═ 8Hz, 2H), 7.66(s, 1H), 7.83-7.95(m, 3H), 8.14(d, J ═ 8Hz, 1H) ms esi (esi): m/e 559(M-H). EXAMPLE 159

According to the same manner as in example 1, from 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-vinylbenzene) sulfonamide (135mg), 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (135mg) was obtained as pale yellow crystals. ¹H-NMR(300MHz.DMSO-d₆) δ: 2.46(s, 3H), 5.11(s, 2H), 5.46(d, J ═ 11Hz, 1H), 5.83(s, 2H), 6.01(d, J ═ 18Hz, 1H), 6.74(d, J ═ 8Hz, 1H), 6.81(dd, J ═ 11, 18Hz, 1H), 6.90-7.03(m, 3H), 7.24-7.36(m, 3H), 7.64-7.75(m, 3H), 7.90(d, J ═ 8Hz, 1H), 7.98(d, J ═ 8Hz, 2H), 8.13(d, J ═ 8Hz, 1H) ms (esi): m/e 571(M-H). example 160

According to the same manner as in example 1, from 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (E) - (2-phenylethylene) sulfonamide (135mg), 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-5- [ (E) - (2-phenylethylene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (152mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.46(s, 3H), 5.60(s, 2H), 5.84(s, 2H), 6.68(d, J ═ 8Hz, 1H), 6.90-7.02(m, 3H), 7.24-7.36(m, 3H), 7.40-7.59(m, 4H), 7.66(s-like, 2H), 7.73-7.82(m, 2H), 7.98(d, J ═ 8Hz, 1H), 8.18(d, J ═ 8Hz, 1H) ms (esi): m/e 571(M-H). EXAMPLE 161

By the same method as in example 1, starting from 3- (2-chloro-4- ((phenoxy) methyl)Benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-chlorothiophene-2-sulfonamide (178mg) to give 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -5- ((5-chlorothiophene-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine as pale yellow crystals (120 mg). ¹H-NMR(300MHz，DMSO-d₆) δ: 2.45(s, 3H), 5.61(s, 2H), 5.83(s, 2H), 6.70(d, J ═ 8Hz, 1H), 6.90-7.02(m, 3H), 7.24-7.35(m, 4H), 7.65(s, 1H), 7.76(d, J ═ 4Hz, 1H), 7.97(d, J ═ 8Hz, 1H), 8.18(d, J ═ 8Hz, 1H) ms (esi): m/e 585, 587 EXAMPLE 162

According to the same manner as in example 1, from 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 5-bromothiophene-2-sulfonamide (178mg), 5- ((5-bromothiophene-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (153mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.45(s, 3H), 5.10(s, 2H), 5.81(s, 2H), 6.69(d, J ═ 8Hz, 1H), 6.90-7.02(m.3h), 7.24-7.35(m, 3H), 7.39(d, J ═ 4Hz, 1H), 7.65(s, 1H), 7.70(d, J ═ 4Hz, 1H), 7.97(d, J ═ 8Hz, 1H), 8.17(d, J ═ 8Hz, 1H) ms esi: m/e 629, 630, 633, example 163

According to the same manner as in example 1, from 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and 1-pentanesulfonamide (111mg), 3- (2-chloro-4- ((phenoxy) methyl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (180mg) was obtained as pale yellow crystals. ¹H-NMR(300MHz，DMSO-d₆) δ: 0.80(t, J ═ 7.5Hz, 3H), 1.17-1.43(m, 4H), 1.63-1.77(m, 2H), 2.48(s, 3H), 3.53(t, J ═ 7.5Hz, 2H), 5.51(s, 2H), 5.83(s, 2H), 6.74(d, J ═ 8Hz, 1H), 6.90-7.04(m, 3H), 7.23-7.48(m, 3H), 7.65(s, 1H), 8.02(d, J ═ 8Hz, 1H), 8.20(d, J ═ 8Hz, 1H) ms (esi): m/e 539(M-1). Example 164

According to the same manner as in example 1The process of (1), from 3- (2-chloro-4- (dimethylaminomethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (115mg) and (4-methylbenzene) sulfonamide (83mg), gives 3- (2-chloro-4- (dimethylaminomethyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine as pale yellow crystals (80 mg).¹H-NMR(300MHz，DMSO-d₆) δ: 2.34(s, 3H), 2.40(s, 6H), 2.46(s, 3H), 3.78(s, 2H), 5.70(s, 2H), 6.60(d, J ═ 8Hz, 1H), 7.23(d, J ═ 8Hz, 1H), 7.30(d, J ═ 8Hz, 2H), 7.60(s, 1H), 7.80(d, J ═ 8Hz, 1H), 7.93(d, J ═ 8Hz, 1H), 8.03(d, J ═ 8Hz, 1H) ms (esi): m/e 512(M + H), example 165

According to the same manner as in example 1, from 3- (2-chloro-4- ((imidazol-1-yl) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (184mg) and (4-methylbenzene) sulfonamide (125mg), 3- (2-chloro-4- ((imidazol-1-yl) methyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (180mg) was obtained as pale yellow crystals. ¹H-NMR(300MHz，DMSO-d₆) δ: 2.39(s, 3H), 2.45(s, 3H), 5.22(s, 2H), 5.77(s, 2H), 6.67(d, J ═ 8Hz, 1H), 6.98(s, 1H), 7.14(d, J ═ 8Hz, 1H), 7.25(s, 1H), 7.40(d, J ═ 8Hz, 2H), 7.48(s, 1H), 7.84-7.93(m, 4H), 8.10(d, J ═ 8Hz, 1H) ms (esi): m/e 533(M-H). Example 166

According to the same manner as in example 1, from 3- (2-chloro-4- ((piperidin-1-yl) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (148mg) and (4-methylbenzene) sulfonamide (96mg), 3- (2-chloro-4- ((piperidin-1-yl) methyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (57mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆)δ：1.43(br peak，2H)，1.55(br peak，4H)，2.34(s，3H)，2.46(s，3H)，2.66(br peak，4H)，3.79(br peak，2H)，5.69(s，2H)，6.56(d，J＝8Hz，1H)，7.23(d，J＝8Hz，1H)，7.29(d，J＝8Hz，2H)，7.58(s，1H)，7.80(d，J＝8Hz，2H)，7.90(d，J＝8Hz，1H)，8.03(d，J＝8Hz, 1H) MS (ESI): m/e 552.2(M + H). Example 167

According to the same manner as in example 1, from 3- (2-chloro-4- (phenylthiomethyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (175mg) and (4-methylbenzene) sulfonamide (107mg), 3- (2-chloro-4- (phenylthiomethyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (119mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.38(s, 3H), 2.41(s, 3H), 4.24(s, 2H), 5.79(s, 2H), 6.68(d, J ═ 8Hz, 1H), 7.12-7.35(M, 6H), 7.43(d, J ═ 8Hz, 1H), 7.54(s, 1H), 7.85-7.98(M, 3H), 8.13(d, J ═ 8Hz, 1H) masks (esi) M/e 575.0(M-H) example 168

According to the same manner as in example 1, from 3- (4- ((benzyloxy) methyl) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-methylbenzene) sulfonamide (123mg), 3- (4- ((benzyloxy) methyl) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (195mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.38(s, 3H), 2.46(s, 3H), 4.53(s, 4H), 5.82(s, 2H), 6.73(d, J ═ 8Hz, 1H), 7.20-7.38(M, 6H), 7.42(d, J ═ 8Hz, 2H), 7.56(s, 1H), 7.85-7.94(M, 3H), 8.13(d, J ═ 8Hz, 1H) masks (esi) M/e 573(M-H) example 169

According to the same manner as in example 1, from 3- (4- (benzimidazol-2-yl) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-methylbenzene) sulfonamide (124mg), 3- (4- (benzimidazol-2-yl) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (140mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: example 170 esi 170 of example 2.34(s, 3H), 2.50(s, 3H), 5.90(s, 2H), 6.98(d, J ═ 8Hz, 1H), 7.20-7.30(M, 2H), 7.38(d, J ═ 8Hz, 2H), 7.57-7.69(M, 2H), 7.86-7.94(M, 3H), 8.06(d, J ═ 8Hz, 1H), 8.16(d, J ═ 8Hz, 1H), 8.37(s, 1H) mass (esi) M/e 569(M-H)

According to the same manner as in example 1, from 2-methyl-3- (4- (1-methylbenzimidazol-2-yl) -2-chlorobenzyl) -3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) and (4-methylbenzene) sulfonamide (120mg), 2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3- (4- (1-methylbenzimidazol-2-yl) -2-chlorobenzyl) -3H-imidazo [ 4, 5-b ] pyridine (81mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.37(s, 3H), 2.53(s, 3H), 3.89(s, 3H), 5.94(s, 2H), 6.90(d, J ═ 8Hz, 1H), 7.21-7.37(M, 3H), 7.42(d, J ═ 8Hz, 2H), 7.65(d, J ═ 8Hz, 1H), 7.70(d, J ═ 8Hz, 1H), 7.78(d, J ═ 8Hz, 1H), 7.90(d, J ═ 8Hz, 2H), 8.09(s, 1H), 8.17(d, J ═ 8Hz, 1H) masks (esi) (585 (M + H) embodiment 171

According to the same manner as in example 1, from 3- ((1-ethylbenzimidazol-2-yl) methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (4-methylbenzene) sulfonamide (139mg), 3- ((1-ethylbenzimidazol-2-yl) methyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (167mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: examples 172.20 (t, J ═ 7.5Hz, 3H), 2.37(s, 3H), 2.65(s, 3H), 4.53(q, J ═ 7.5Hz, 2H), 6.10(s, 2H), 7.17(t, J ═ 8Hz, 1H), 7.26(t, J ═ 8Hz, 1H), 7.42(d, J ═ 8Hz, 2H), 7.53(d, J ═ 8Hz, 1H), 7.60(d, J ═ 8Hz, 1H), 7.87(d, J ═ 8Hz, 1H), 7.90(d, J ═ 8Hz, 1H), 8.12(d, J ═ 8Hz, 1H) masses (esi) M/e 487.2(M-H), 172.

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and 1-pentanesulfonamide (106mg), 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (174mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆)δ：0.79(t，J＝7.5Hz，3H)，1.10-1.45(m，4H)，1.56-1.81(m，2H)，2.50(s，3H)，3.43-3.63(m，2H)，5.83(s，2H)，6.80(d，J＝8Hz，1H)，7.Example 173 (t, J ═ 5Hz, 1H), 7.50(d, J ═ 8Hz, 1H), 7.55-7.70(M, 2H), 7.86(s-like, 1H), 8.03(d, J ═ 8Hz, 1H), 8.21(d, J ═ 8Hz, 1H) mass (esi) M/e 515.2(M-H)

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (4-methylbenzene) sulfonamide (120mg), 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (199mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.37(s, 3H), 2.50(s, 3H), 5.84(s, 2H), 6.80(d, J ═ 8Hz, 1H), 7.16(t, J ═ 5Hz, 1H), 7.40(d, J ═ 8Hz, 2H), 7.53(dd, J ═ 8, 2Hz, 1H), 7.58-7.65(M, 2H), 7.82-7.94(M, 4H), 8.13(d, J ═ 8Hz, 1H) masks (esi) M/e 535.1(M-H) example 174 (M-H)

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and 5-chlorothiophene-2-sulfonamide (139mg), 3- (2-chloro-4- (thiophen-2-yl) benzyl) -5- ((5-chlorothiophen-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (194mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.50(s, 3H), 5.83(s, 2H), 6.75(d, J ═ 8Hz, 1H), 7.15(t, J ═ 5Hz, 1H), 7.28(d, J ═ 4Hz, 1H), 7.51(dd, J ═ 8.2Hz, 1H), 7.56-7.65(m, 2H), 7.74(d, J ═ 4Hz, 1H), 7.88(d, J ═ 2Hz, 1H), 7.98(d, J ═ 8Hz, 1H), 8.17(d, J ═ 8Hz, 1H) masss (esi) 175 m/e 561.0 example 175 m/e 561.0

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and 5-bromothiophene-2-sulfonamide (170mg), 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (228mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆)δ：2.50(s，3H)，5.83(s，2H)，6.75(d，J＝8Hz，1H)，7.14(t，J＝5Hz, 1H), 7.37(d, J ═ 4Hz, 1H), 7.52(dd, J ═ 8.2Hz, 1H), 7.57-7.64(m, 2H), 7.70(d, J ═ 4Hz, 1H), 7.87(d, J ═ 2Hz, 1H), 7.98(d, J ═ 8Hz, 1H), 8.17(d, J ═ 8Hz, 1H) masks (esi) m/e 606.7 example 176

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (E) - (2-phenylethene) sulfonamide (129mg), 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-5- ((E) - (2-phenylethenyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (199mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.50(s, 3H), 5.85(s, 2H), 6.71(d, J ═ 8Hz, 1H), 7.15(t, J ═ 5Hz, 1H), 7.36-7.82(M, 10H), 7.88(d, J ═ 2Hz, 1H), 7.98(d, J ═ 8Hz, 1H), 8.18(d, J ═ 8Hz, 1H) masks (esi) M/e 547.1(M-H) example 177

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (4-vinylbenzene) sulfonamide (129mg), 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (194mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.58(s, 3H), 5.45(d, J ═ 11Hz, 1H), 5.83(s, 2H), 6.01(d, J ═ 19Hz, 1H), 6.72-6.90(M, 2H), 7.16(t, J ═ 5Hz, 3H, 7.55(dd, J ═ 8, 2Hz, 1H), 7.58-7.65(M, 2H), 7.69(d, J ═ 8Hz, 1H), 7.84-7.92(M, 2H), 7.97(d, J ═ 8Hz, 2H), 8.14(d, J ═ 8Hz, 1H) masss (esi) M/e 547.1(M-H) example 178 (M-H), 7.97(d, J ═ 8Hz, 1H) mass (esi) M/e 547.1(M-H)

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and 1-pentanesulfonamide (98mg), 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (177mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆)δ：0.79(t，J＝7.5Hz，3H)，1.14-1.41(m，4H) 1.60-1.75(m, 2H), 2.51(s, 3H), 3.51(t, J ═ 7.5Hz, 2H), 5.83(s, 2H), 6.78(d, J ═ 8Hz, 1H), 7.18(d, J ═ 4Hz, 1H), 7.41(dd, J ═ 8.2Hz, 1H), 7.50(d, J ═ 4Hz, 1H), 7.85(d, J ═ 2Hz, 1H), 8.01(d, J ═ 8Hz, 1H), 8.19(d, J ═ 8Hz, 1H) mass (esi) m/e 549.0 example 179

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (4-methylbenzene) sulfonamide (111mg), 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (179mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.37(s, 3H), 2.50(s, 3H), 5.83(s, 2H), 6.78(d, J ═ 8Hz, 1H), 7.20(d, J ═ 4Hz, 1H), 7.40(d, J ═ 8Hz, 2H), 7.48(dd, J ═ 8.2Hz, 1H), 7.52(d, J ═ 4Hz, 1H), 7.83-7.95(m, 4H), 8.15(d, J ═ 8Hz, 1H) masss (esi) m/e 569.2 example 180

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and 5-chlorothien-2-sulfonamide (128mg), 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (182mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: examples 2.50(s, 3H), 5.82(s, 2H), 6.73(d, J ═ 8Hz, 1H), 7.18(d, J ═ 4Hz, 1H), 7, 29(d, J ═ 8Hz, 1H), 7.45(dd, J ═ 8, 2Hz, 1H), 7.51(d, J ═ 4Hz, 1H), 7.76(d, J ═ 4Hz, 1H), 7.86(d, J ═ 2Hz, 1H), 7.98(d, J ═ 8Hz, 1H), 8.17(d, J ═ 8Hz, 1H) masks (esi) m/e 595.1, 597.0, 599.0 examples 181 (s, J ═ 8Hz, 1H), 8.17(d, J ═ 8Hz, 1H) m/e 595.1, 597.0, 599.0

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and 5-bromothiophene-2-sulfonamide (156mg), 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -amide was obtained as pale yellow crystals) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (207 mg).¹H-NMR(300MHz，DMSO-d₆) δ: 2.50(s, 3H), 5.82(s, 2H), 6.74(d, J ═ 8Hz, 1H), 7.19(d, J ═ 4Hz, 1H), 7.38(d, J ═ 4Hz, 1H), 7.47(dd, J ═ 8.2Hz, 1H), 7.51(d, J ═ 4Hz, 1H), 7.70(d, J ═ 4Hz, 1H), 7.87(d, J ═ 2Hz, 1H), 7.98(d, J ═ 8Hz, 1H), 8.18(d, J ═ 8Hz, 1H) mass (esi) m/e 639.1, 641.3, 643.5, 182, m/e 639.1, 641.3, 643.5, and others

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (E) - (2-phenylethene) sulfonamide (118mg), 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-5- ((E) - (2-phenylethene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (182mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.50(s, 3H), 5.84(s, 2H), 6.72(d, J ═ 8Hz, 1H), 7.18(d, J ═ 4Hz, 1H), 7.35-7.60(m, 6H), 7.60-7.84(m, 3H), 7.86(d, J ═ 2Hz, 1H), 7.98(d, J ═ 8Hz, 1H), 8.17(d, J ═ 8Hz, 1H) masks (esi) m/e 581.0, 583.2 example 183

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg) and (4-vinylbenzene) sulfonamide (118mg), 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2-methyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (180mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.49(s, 3H), 5.46(d, J ═ 11Hz, 1H), 5.83(s, 2H), 6.01(d, J ═ 18Hz, 1H), 6.70-6.98(m, 2H), 7.20(d, J ═ 4Hz, 1H), 7.46(dd, J ═ 8, 2Hz, 1H), 7.52(d, J ═ 4Hz, 1H), 7.70(d, J ═ 8Hz, 2H), 7.83-7.92(m, 2H), 7.96(d, J ═ 8Hz, 2H), 8.14(d, J ═ 8Hz, 1H) masss (esi) m/e 581.2 example 184

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg), colorless crystals of 3- (2-chloro-4-phenyl) were obtainedBenzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (165 mg). mp 227-¹H-NMR(CDCl₃): 0.85(3H, t, J ═ 8Hz), 1.21-1.44(4H, M), 1.78-1.90(2H, M), 2.67(3H, s), 2.75(3H, s), 3.49-3.56(2H, M), 5.60(2H, s), 6.76(1H, d, J ═ 8Hz), 7.33-7.47(3H, M), 7.52-7.57(2H, M), 7.70(1H, d, J ═ 1Hz), 8.01(1H, s), 9.87(1H, brs) mass (esi) M/z 523(M-1) examples 185 (M-1)

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg), colorless crystals of 3- (2-chloro-4-phenylbenzyl) -5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine (177mg) were obtained. mp 241-¹H-NMR(CDCl₃): 2.67(3H, s), 2.72(3H, s), 5.59(2H, s), 6.81(1H, d, J ═ 8Hz), 6.90(1H, d, J ═ 5Hz), 7.35-7.49(4H, M), 7.54-7.58(2H, M), 7.67-7.72(2H, M), 7.96(1H, s) mass (esi) M/z 571(M +1) example 186

The same procedures used in example 1 were repeated except for using 3- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) to give 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine (175mg) as colorless crystals. mp 243 plus 244 deg.C¹H-NMR(CDCl₃): 2.67(3H, s), 2.71(3H, s), 5.59(2H, s), 6.81(1H, d, J ═ 8Hz), 7.03(1H, d, J ═ 5Hz), 7.35-7.49(4H, M), 7.56(2H, d, J ═ 8Hz), 7.65(1H, d, J ═ 5Hz), 7.71(1H, d, J ═ 1Hz), 7.95(1H, s) mass esi) M/z 615(M-1) example 187 (M-1)

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg), colorless crystals of 3- (2-chloro-4-phenylbenzyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (180mg) were obtained. mp 220-¹H-NMR(CDCl₃)：266(3H, s), 2.68(3H, s), 5.41(1H, d, J-10 Hz), 5.60(2H, s), 5.83(1H, d, J-18 Hz), 6.65(2H, dd, J-18.10 Hz), 6.81(1H, d, J-8 Hz), 7.35-7.50(6H, M), 7.57(2H, d, J-8 Hz), 7.72(1H, d, J-1 Hz), 7.90(1H, s), 8.04(2H, d, J-8 Hz) mass (esi) M/z 555(M-1) example 188 (M-1)

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg), colorless crystals of 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (165mg) were obtained. mp 220-¹H-NMR(CDCl₃): 0.85(3H, t, J ═ 8Hz), 1.20-1.44(4H, M), 1.75-1.90(2H, M), 2.65(3H, s), 2.74(3H, s), 3.47-3.56(2H, M), 5.56(2H, s), 6.73(1H, d, J ═ 8Hz), 7.08(1H, t, J ═ 4Hz), 7.28-7.34(2H, M), 7.40(1H, br d, J ═ 8Hz), 7.70(1H, s), 8.01(1H, s), 9.85(1H, br) mass (esi) M/z 529(M-1) examples 189 and 189

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (187mg) were obtained. mp 224 and 226 deg.C¹H-NMR(CDCl₃): 2.39(3H, s), 2.69(3H, s), 2.68(3H, s), 5.56(2H, s), 6.79(1H, d, J ═ 8Hz), 7.10(1H, t, J ═ 4Hz), 7.20-7.38(3H, M), 7.45(1H, br d, J ═ 8Hz), 7.72(1H, d, J ═ 1Hz), 7.89(1H, s), 7.95-8.02(2H, M), 10.10(1H, br) masss (esi) M/z 549(M-1) example 190

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 5- ((5-bromothiophen-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine (199mg) were obtained. mp 246-248 deg.C¹H-NMR(CDCl₃): 2.66(3H, s), 2.70(3H, s), 5.55(2H, s), 6.79(1H, d, J ═ 8Hz), 7.03(1H, d, J ═ 4Hz), 7.10(1H, t, J ═ 4Hz), 7.33-7.36(2H, M), 7.45(1H, dd, J ═ 8.1Hz), 7.65(1H, d, J ═ 4Hz), 7.71(1H, s), 7.94(1H, s), 10.19(1H, brs) masss (esi) M/z 620(M-1) examples 191

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-5- ((E) - (2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (196mg) were obtained. mp 216 + 217 deg.C¹H-NMR(CDCl₃): 2.64(3H, s), 2.72(3H, s), 5.57(2H, s), 6.72(1H, d, J ═ 8Hz), 7.08-7.11(2H, M), 7.30-7.52(8H, M), 7.71(1H, d, J ═ 1Hz), 7.77(1H, d, J ═ 15Hz), 7.98(1H, s), 10.06(1H, brs) masks (esi) M/z 561(M +1) example 192 (M +1) or (c/e)

According to the same manner as in example 1, from 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4- (thiophen-2-yl) benzyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (187mg) were obtained. mp 220-¹H-NMR(CDCl₃): 2.65(3H, s), 2.68(3H, s), 5.41(1H, d, J ═ 11Hz), 5.56(2H, s), 5.84(1H, d, J ═ 18Hz), 6.70(2H, dd, J ═ 18.11Hz), 6.79(1H, d, J ═ 8Hz), 7.11(1H, t, J ═ 4Hz), 7.32-7.37(2H, m), 7.42-7.48(3H, m), 7.72(1H, d, J ═ 1Hz), 7.89(1H, s), 8.04(2H, d, J ═ 8Hz), 10.13(1H, s) example 193

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (187mg) were obtained. mp 215 + 217 deg.C¹H-NMR(CDCl₃)：0.86(3H, t, J ═ 8Hz), 1.23-1.45(4H, M), 1.77-1.90(2H, M), 2.65(3H, s), 2.74(3H, s), 3.47-3.56(2H, M), 5.55(2H, s), 6.74(1H, d, J ═ 8Hz), 6.89(1H, t, J ═ 4Hz), 7.09(1H, d, J ═ 4Hz), 7.31(1H, dd, J ═ 8.1Hz), 7.59(1H, d, J ═ 1Hz), 8.01(1H, s), 9.82(1H, brs) massesi (563) M/z (M-1) example 194

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (178mg) were obtained. mp 240 and 241 deg.C¹H-NMR(CDCl₃): 2.40(3H, s), 2.64(3H, s), 2.68(3H, s), 5.55(2H, s), 6.76(1H, d, J ═ 81Hz), 6.91(1H, d, J ═ 4Hz), 7.12(1H, d, J ═ 4Hz), 7.23-7.37(3H, M), 7.61(1H, d, J ═ 1Hz), 7.89(1H, s), 7.99(2H, d, J ═ 8Hz), 10.08(1H, brs) mass (esi) M/z 583(M-1) example 195

From 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine (175mg) were obtained according to the same manner as in example 1. mp 252 and 253 deg.C¹H-NMR(CDCl₃): example 196.66 (3H, s), 2.70(3H, s), 5.54(2H, s), 6.78(1H, d, J ═ 8Hz), 6.91(1H, d, J ═ 4Hz), 7.04(1H, d, J ═ 4Hz), 7.11(1H, d, J ═ 4Hz), 7.33(1H, dd, J ═ 8.1Hz), 7.60(1H, brs), 7.67(1H, d, J ═ 4Hz), 7.94(1H, s), 10.18(1H, brs) mass (esi) M/z 654(M-1)

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-5- ((E) - (2-phenylvinyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-c-l-b ] pyridine (208 mg). mp 224-¹H-NMR(CDCl₃): examples 197 (M-1) of embodiment 64(3H, s), 2.72(3H, s), 5.55(2H, s), 6.72(1H, d, J-8 Hz), 6.90(1H, d, J-4 Hz), 7.09(1H, d, J-4 Hz), 7.12(1H, d, J-8 Hz), 7.32(1H, dd, J-8, 1Hz), 7.35-7.44(3H, M), 7.47-7.52(2H, M), 7.60(1H, d, J-1 Hz), 7.77(1H, d, J-15 Hz), 7.98(1H, s), 10.03(1H, brs) mass (esi) M/z (595M-1)

According to the same manner as in example 1, from 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4- (5-chlorothien-2-yl) benzyl) -2, 7-dimethyl-5- ((4-vinylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (184mg) were obtained. mp 217 + 218 deg.C¹H-NMR(CDCl₃): 2.65(3H, s), 2.68(3H, s), 5.42(1H, d, J ═ 11Hz), 5.55(2H, s), 5.86(1H, d, J ═ 18Hz), 6.65-6.80(2H, M), 6.92(2H, d, J ═ 4Hz), 7.12(1H, d, J ═ 4Hz), 7.33(1H, dd, J ═ 8.1Hz), 7.28(2H, d, J ═ 8Hz), 7.62(1H, d, J ═ 1Hz), 7.89(1H, s), 8.05(2H, d, J ═ 8Hz), 10.10(1H, s) mass esi (M/z 595(M-1), 198

According to the same manner as in example 1, from 3- (2-chloro-4- (n-pentylthio) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (170mg), colorless crystals of 3- (2-chloro-4- (n-pentylthio) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (186mg) were obtained. mp 153-¹H-NMR(CDCl₃): 0.91(3H, t, J ═ 7.5Hz), 1.25-1.48(4H, M), 1.55-1.73(2H, M), 2.42(3H, s), 2.63(3H, s), 2.94(2H, t, J ═ 7.5Hz), 5.53(2H, s), 6.68(1H, d, J ═ 8Hz), 7.12(1H, dd, J ═ 8, 1Hz), 7.27-7.40(3H, M), 8.00-8.10(4H, M) masss (esi) M/z (M +1) examples 199/z (M557, M)

According to the same method as in example 1, from 3- (4- (benzylthio) -2-chloro) benzyl-2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (4- (benzylthio) -2-chloro) benzyl were obtainedYl-2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (156 mg). mp 165-166 deg.C¹H-NMR(CDCl₃): 2.42(3H, s), 2.60(3H, s), 4.15(2H, s), 5.52(2H, s), 6.65(1H, d, J ═ 8Hz), 7.12(1H, dd, J ═ 8.1Hz), 7.21-7.36(7H, M), 7.39(1H, d, J ═ 1Hz), 8.01-8.10(4H, M) mass (esi) M/z 577(M +1) example 200

According to the same manner as in example 1, from 3- (2-chloro-4- ((3-pyridyloxy) methyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (160mg) and (4-methylbenzene) sulfonamide (101mg), 3- (2-chloro-4- ((3-pyridyloxy) methyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (159mg) was obtained as pale yellow crystals.¹H-NMR(300MHz，DMSO-d₆) δ: 2.38(s, 3H), 2.46(s, 3H), 5.19(s, 2H), 5.84(s, 2H), 6.75(d, J ═ 8Hz, 1H), 7.23-7.38(M, 2H), 7.38-7.49(M, 3H), 7.70(s, 1H), 7.84-7.94(M, 3H), 8.13(d, J ═ 8Hz, 1H), 8.18(dd, J ═ 5.2Hz, 1H), 8.35(d, J ═ 2Hz, 1H) masss (esi) M/e 562.1(M + H) example 201

According to the same manner as in example 1, from 3- (2-chloro-4-ethylsulfanylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4-ethylsulfanylmethyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (156mg) were obtained. mp 162-¹H-NMR(CDCl₃): 1.35(3H, t, J ═ 7.5Hz), 2.42(3H, s), 2.63(3H, s), 2.97(2H, q, J ═ 7.5Hz), 5.53(2H, s), 6.69(1H, d, J ═ 8Hz), 7.13(1H, dd, J ═ 8, 1Hz), 7.33(2H, d, J ═ 8Hz), 7.39(1H, d, J ═ 1Hz), 8.01-8.10(4H, M) masks (esi) M/z 360(M-1) example 202

According to the same manner as in example 1, from 3- (4- (N-butyrylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (210mg) and (4-methylbenzene) sulfonamide (232mg), colorless crystals of 3- (4- (N-butyrylamino) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazole were obtainedAnd [ 4, 5-b ] pyridine (225 mg).¹H-NMR(CDCl₃)：1.00(3H，t，J＝7Hz)，1.69-1.81(2H，m)，2.35(2H，t，J＝7Hz)，2.42(3H，s)，2.64(3H，s)，5.51(2H，s)，6.84(1H，d，J＝8Hz)，7.25(1H，d，J＝7Hz)，7.33(1H，d，J＝7Hz)，7.40(1H，s)，7.97-8.03(5H，m)Mass(ESI)m/z 538(M-H)^-mp 242-246 ℃ example 203

According to the same manner as in example 1, from 3- (4- (N-benzoylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (150mg) and (4-methylbenzene) sulfonamide (153mg), colorless crystals of 3- (4- (N-benzoylamino) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (139mg) were obtained.¹H-NMR(CDCl₃)：2.40(3H，s)，2.69(3H，s)，5.57(2H，s)，6.97(1H，d，J＝8Hz)，7.31(2H，d，J＝7Hz)，7.46-7.58(4H，m)，7.90(2H，d，J＝8Hz)，7.98-8.11(4H，m)Mass(ESI)m/z 572(M-H)^-mp 270-

According to the same manner as in example 1, from 3- (4- (N-benzoyl-N-methylamino) -2-chlorobenzyl methyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (225mg) and (4-methylbenzene) sulfonamide (221mg), 3- (4- (N-benzoyl-N-methylamino) -2-chlorobenzyl methyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (227mg) was obtained as a pale yellow powder. ¹H-NMR(CDCl₃)：2.43(3H，s)，2.53(3H，s)，3.49(3H，s)，5.52(2H，s)，6.54(1H，d，J＝8Hz)，6.85(1H，d，J＝8Hz)，7.18-7.37(8H，m)，8.03-8.10(4H，m)Mass(ESI)m/z 586(M-H)^-Example 2055- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine sodium salt

To 5- (benzenesulfonylcarbamoyl) -3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1.0g) was added N, N-dimethylformamide (33ml), and the mixture was heated to 80 ℃. The crystals remaining after dissolution were filtered, washed with N, N-dimethylformamide (3ml), and stirred at room temperatureAnd (4) stirring. 12ml of 1N NaOH was added thereto at room temperature, and the mixture was stirred for 30 minutes. The precipitated crystals were collected by filtration, washed with N, N-dimethylformamide/water 3/1 and water. Drying at 60 ℃ under reduced pressure for 8 hours gave the desired product as colorless crystals (600 mg).¹H-NMR(DMSO-d₆): 2.49(3H, s), 5.59(2H, s), 6.49(1H, d, J ═ 8Hz), 7.32-7.51(7H, m), 7.65(2H, d, J ═ 8Hz), 7.80-7.86(3H, m), 7.94(1H, d, J ═ 8Hz), 8.01(1H, d, J ═ 8Hz) masss (esi) m/z 515 example 206/z 515

From 5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1g), colorless crystals of sodium 5- [ (4-vinylbenzene) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzylmethyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (532mg) were obtained in the same manner as in example 205. ¹H-NMR(DMSO-d₆): 2.49(3H, s), 5.30(1H, d, J ═ 10Hz), 5.59(2H, s), 5.86(1H, d, J ═ 17Hz), 6.50(1H, d, J ═ 8Hz), 6.74(1H, dd, J ═ 17.10Hz), 7.34-7.52(6H, M), 7.64(2H, d, J ═ 8Hz), 7.75-7.85(3H, M), 7.93(1H, d, J ═ 8Hz), 8.00(1H, d, J ═ 8Hz) masss (esi) M/z 541(M-1) mp > 300 ℃ example 207 ℃, (M-1) mp > 300 ℃

According to the same manner as in example 205, from 5- [ (5-bromothien-2-yl) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1.2g), colorless crystals of sodium 5- [ (5-bromothien-2-yl) sulfonylcarbamoyl ] -3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine (1.02g) were obtained.¹H-NMR(DMSO-d₆): 2.49(3H, s), 5.62(2H, s), 6.51(1H, d, J ═ 8Hz), 7.08(1H, d, J ═ 5Hz), 7.29(1H, d, J ═ 3Hz), 7.34-7.53(4H, m), 7.67(2H, d, J ═ 8Hz), 7.85(1H, s), 7.96(1H, d, J ═ 8Hz), 8.01(1H, d, J ═ 8Hz) mp > 250 ℃ example 208 ℃

From 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine (1g), colorless crystals were obtained as in example 205 Bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- [ (4-methylbenzene) sulfonylcarbamoyl ] -3H-imidazo [ 4, 5-b ] pyridine sodium (972 mg).¹H-NMR(DMSO-d₆): 2.30(3H, s), 2.43(3H, s), 2.56(3H, s), 5.48(2H, s), 6.35(1H, d, J ═ 8Hz), 7.17(2H, d, J ═ 8Hz), 7.40(1H, d, J ═ 8Hz), 7.71(2H, d, J ═ 8Hz), 7.83(2H, s) mp > 250 ℃ example 209

According to the same manner as in example 1, from 3- (4- (N-butyryl-N-methylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (90mg) and (4-methylbenzene) sulfonamide (96mg), 3- (4- (N-butyryl-N-methylamino) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (58mg) was obtained as a pale yellow powder.¹H-NMR(CDCl₃)：0.87(3H，t，J＝7Hz)，1.56-1.69(2H，m)，2.12(2H，br)，2.43(3H，s)，2.63(3H，s)，3.27(3H，s)，5.61(2H，s)，6.68(1H，d，J＝8Hz)，7.03(1H，dd，J＝8.2Hz)，7.30-7.39(3H，m)，8.04-8.13(4H，m)，10.09(1H，s)Mass(ESI)：m/z 552(M-H)^-Example 210

According to the same manner as in example 1, from 3- (2-chloro-4- (N- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (170mg) and (4-methylbenzene) sulfonamide (188mg), 3- (2-chloro-4- (N- (N-pentyl) amino) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (189mg) was obtained as colorless crystals.¹H-NMR(CDCl₃)：0.91(3H，t，J＝7Hz)，1.34-1.42(4H，m)，1.57-1.62(2H，m)，2.42(3H，s)，2.66(3H，s)，3.05-3.13(2H，m)，3.83(1H，br)，5.45(2H，s)，6.48(1H，dd，J＝8，2Hz)，6.65(1H，d，J＝2Hz)，6.79(1H，d，J＝8Hz)，7.33(2H，d，J＝8Hz)，7.97-8.05(4H，m)，10.14(1H，s)Mass(ESI)：m/z 538(M-H)^-mp 222-

According to the same manner as in example 1, from 3- (2-chloro-4- (N-methyl-N- (N-pentyl) amino) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (45mg) and (4)-methylbenzene) sulfonamide (48mg) to give colorless crystals of 3- (2-chloro-4- (N-methyl-N- (N-pentyl) amino) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (12 mg).¹H-NMR(CDCl₃)：0.90(3H，t，J＝7Hz)，1.15-1.45(4H，m)，1.55-1.65(2H，m)，2.42(3H，s)，2.67(3H，s)，2.94(3H，s)，5.47(2H，s)，6.53(1H，d，J＝8Hz)，6.70(1H，s)，6.81(1H，d，J＝8Hz)，7.27-7.35(2H，m)，7.98-8.04(4H，m)，10.18(1H，s)Mass(ESI)：m/z 552(M-H)^-mp 175-

According to the same manner as in example 1, from 3- (4- (N-benzenesulfonylamino) -2-chlorobenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (165mg) and (4-methylbenzene) sulfonamide (155mg), colorless crystals of 3- (4- (N-benzenesulfonylamino) -2-chlorobenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (157mg) were obtained.¹H-NMR(DMSO-d₆)：2.37(3H，s)，2.39(3H，s)，5.70(2H，s)，6.72(1H，d，J＝8Hz)，7.00(1H，d，J＝8Hz)，7.24(1H，s)，7.42(2H，d，J＝8Hz)，7.55-7.65(3H，m)，7.77(2H，d，J＝8Hz)，7.83-7.92(3H，m)，8.09(1H，d，J＝8Hz)Mass(ESI)：m/z 608(M-H)^-mp 234-

According to the same manner as in example 1, from 3- (2-chloro-4- (isopropoxycarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (250mg) and (4-methylbenzene) sulfonamide (331mg), colorless crystals of 3- (2-chloro-4- (isopropoxycarbonyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (133mg) were obtained. ¹H-NMR(CDCl₃)：1.36(3H，s)，1.38(3H，s)，2.42(3H，s)，2.59(3H，s)，5.20-5.32(1H，m)，5.64(2H，s)，6.71(1H，d，J＝8Hz)，7.33(2H，d，J＝8Hz)，7.85(1H，dd，J＝8，2Hz)，8.02-8.16(5H，m)，10.07(1H，s)Mass(ESI)：m/z 539(M-H)^-mp 199-

By the same method as in example 1, from 3- (2-chloro-4- (cyclohexyloxy)Alkylcarbonyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (289mg) and (4-methylbenzene) sulfonamide (231mg) gave 3- (2-chloro-4- (cyclohexyloxycarbonyl) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (312mg) as colorless crystals.¹H-NMR(CDCl₃)：1.32-1.65(6H，m)，1.78(2H，brs)，1.92(2H，brs)，2.42(3H，s)，2.59(3H，s)，4.99-5.06(1H，m)，5.64(2H，s)，6.71(1H，d，J＝8Hz)，7.73(2H，d，J＝8Hz)，7.86(1H，d，J＝8Hz)，8.02-8.16(5H，m)，10.09(1H，s)Mass(ESI)：m/z 579(M-H)^-Example 215

According to the same manner as in example 1, from 3- (2-chloro-4- (3-phenylureido) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (207mg) and (4-methylbenzene) sulfonamide (244mg), 3- (2-chloro-4- (3-phenylureido) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (60mg) was obtained as colorless crystals.¹H-NMR(CDCl₃)：2.38(3H，s)，2.68(3H，s)，5.52(2H，s)，6.93(1H，d，J＝8Hz)，7.05(1H，t，J＝7Hz)，7.22(1H，dd，J＝8.2Hz)，7.27-7.33(4H，m)，7.42(2H，d，J＝8Hz)，7.87(1H，d，J＝2Hz)，7.98-8.02(5H，m)，8.28(1H，s)Mass(ESI)：m/z 587(M-H)^-Example 216

According to the same manner as in example 1, from 3- (2-chloro-4-propoxybenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg), colorless crystals of 3- (2-chloro-4-propoxybenzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (213mg) were obtained.¹H-NMR(CDCl₃): 1.04(3H, t, J ═ 7Hz), 1.74-1.88(2H, m), 2.42(3H, s), 2.63(3H, s), 3.93(2H, t, J ═ 7Hz), 5.51(2H, s), 6.78(2H, s), 7.02(1H, s), 7.32(1H, s), 7.35(1H, s), 8.00-8.10(4H, m), 10.12(1H, brs) mass (esi): m/z 511(M-1) mp 144-146 ℃ example 217

By the same method as in example 1, from 3- (2-chloro-4- (n-pentyloxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ]Pyridine-5-carboxylic acid (200mg) to give colorless crystals of 3- (2-chloro-4- (n-pentyloxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (231 mg).¹H-NMR(CDCl₃): 0.93(3H, t, J ═ 7Hz), 1.30-1.50(6H, m), 1.73-1.85(2H, m), 2.42(3H, s), 2.64(3H, s), 3.95(2H, t, J ═ 7Hz), 5.51(2H, s), 6.78(2H, s), 7.02(1H, s), 7.32(1H, s), 7.35(1H, s), 8.00-8.10(4H, m), 10.12(1H, brs) mass (esi): m/z 539(M-1) mp 162-

According to the same manner as in example 1, from 3- (2-chloro-4-ethoxy) benzyl-2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (280mg), colorless crystals of 3- (2-chloro-4-ethoxy) benzyl-2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (318mg) were obtained.¹H-NMR(CDCl₃): 1.42(3H, t, J ═ 7.5Hz), 2.43(3H, s), 2.64(3H, s), 4.04(2H, q, J ═ 7Hz), 5.51(2H, s), 6.78(1H, s), 6.79(1H, s), 7.02(1H, brs), 7.34(1H, d, J ═ 8Hz), 8.00-8.09(4H, m), 10.11(1H, brs) mass (esi): m/z 497(M-1) mp 190-

According to the same manner as in example 1, from 3- (2-chloro-4- (2-methoxyethoxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (189mg), colorless crystals of 3- (2-chloro-4- (2-methoxyethoxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (203mg) were obtained.¹H-NMR(CDCl₃): 2.43(3H, s), 2.64(3H, s), 3.46(3H, s), 3.70-3.80(2H, m), 4.08-4.18(2H, m), 5.52(2H, s), 6.74-6.87(2H, m), 7.07(1H, brs), 7.35(2H, d, J ═ 8Hz), 7.99-8.10(4H, m) mass (esi): m/z 527(M-1) mp 156-158 ℃ example 220

According to the same manner as in example 1, from 3- (2-chloro-4- ((thiophen-2-yl) methoxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (180mg), colorless crystals of 3- (2-chloro-4- ((thiophen-2-yl) methoxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) were obtained-3H-imidazo [ 4, 5-b ] pyridine (215 mg).¹H-NMR(CDCl₃): 2.42(3H, s), 2.64(3H, s), 5.23(2H, s), 5.52(2H, s), 6.81(1H, d, J ═ 8Hz), 6.88(1H, dd, J ═ 8.2Hz), 7.02(1H, dd, J ═ 5.3Hz), 7.10-7.14(2H, m), 7.30-7.36(3H, m), 8.00-8.10(4H, m), 10.09(1H, brs) mass (esi): m/z 565(M-1) mp 184-

According to the same manner as in example 1, from 3- (2-chloro-4- ((thiophen-3-yl) methoxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (115mg), colorless crystals of 3- (2-chloro-4- ((thiophen-3-yl) methoxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (126mg) were obtained.¹H-NMR(CDCl₃): 2.42(3H, s), 2.64(3H, s), 5.08(2H, s), 5.52(2H, s), 6.81(1H, d, J ═ 8Hz), 6.87(1H, dd, J ═ 8.2Hz), 7.11(1H, d, J ═ 2Hz), 7.14(1H, br d, J ═ 5Hz), 7.28-7.39(4H, m), 8.00-8.09(4H, d, J ═ 8Hz) masss (esi): m/z 565(M-1) mp 198-

According to the same manner as in example 1, from 3- (2-chloro-4-phenylvinyl) benzyl-2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (125mg), colorless crystals of 3- (2-chloro-4-phenylvinyl) benzyl-2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (123mg) were obtained.¹H-NMR(CDCl₃): 2.39(3H, s), 2.62(3H, s), 2.69(3H, s), 5.58(2H, s), 6.70(1H, br d, J ═ 8Hz), 7.12(1H, dd, J ═ 8.1Hz), 7.23-7.43(6H, m), 7.48-7.58(2H, m), 7.65(1H, brs), 7.91(1H, brs), 8.00-8.01(2H, m), 10.10(1H, brs) mass (esi): m/z 567(M-1) mp 221-

According to the same manner as in example 1, from 3- (2-chloro-4- (cyclopentylmethoxy) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (69mg), 3- (2-chloro-4- (cyclopentylmethoxy) benzyl) -2-methyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (66mg) was obtained as colorless crystals.¹H-NMR(CDCl₃): 1.36-1.44(2H, m), 1.50-1.71(3H, m), 1.75-1.91(2H, m), 2.35(1H, m), 2.42(3H, s), 2.64(3H, s), 3.83(2H, d, J ═ 5Hz), 5.51(2H, s), 6.78(2H, s), 6.02(1H, brs), 7.33(2H, d, J ═ 8Hz), 7.98-8.10(4H, m) mass (esi): m/z 551(M-1) mp 177-

The same procedures used in example 1 were repeated except for using 3- (2-chloro-4-phenylvinyl) benzyl-2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (200mg) to give 3- (2-chloro-4-phenylvinyl) benzyl-2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (204mg) as colorless crystals.¹H-NMR(CDCl₃): 0.86(3H, t, J ═ 8Hz), 1.25-1.48(4H, m), 1.81-1.96(2H, m), 2.62(3H, s), 2.75(3H, s), 3.49-3.61(2H, m), 5.57(2H, s), 6.65(1H, d, J ═ 8Hz), 7.29-7.41(4H, m), 7.48-7.56(2H, m), 7.65(1H, brs), 8.03(1H, s), 9.85(1H, brs) mass (esi): m/z 547(M-1) mp 201-

According to the same manner as in example 1, from 3- (2-chloro-4- (1-hexynyl) benzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (400mg), colorless crystals of 3- (2-chloro-4- (1-hexynyl) benzyl) -2-methyl-5- (N- (4-methylbenzenesulfonyl) carbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (448mg) were obtained.¹H-NMR(CDCl₃): 0.95(3H, t, J ═ 6Hz), 1.40-1.65(4H), 2.35-2.48(5H), 2.60(3H, s), 5.57(2H, s), 6.65(1H, d, J ═ 8Hz), 7, 22(1H, d, J ═ 8Hz), 7.34(2H, d, J ═ 8Hz), 7.52(1H, s), 8.02-8.12(4H) mp 175-

According to the same manner as in example 1, from 3- (2-chloro-4- (cyclohexylmethoxy) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (254mg) and 1-pentanesulfonamide (135mg), colorless crystals of 3- (2-chloro-4- (cyclohexylmethoxy) benzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (240mg) were obtained.¹H-NMR(CDCl₃)：0.89(3H，t，J＝7Hz)，0.96-1.93(17H，m)，2.64(3H，s)，2.73(3H，s)，3.55(2H，m), 3.72(2H, d, J ═ 7Hz), 5.48(2H, s), 6.71(2H, brs), 6.98(1H, d, J ═ 1Hz), 7.99(1H, s) mass (esi): m/z 559(M-1) example 227

According to the same manner as in example 1, from 3- (2-chloro-4- (cyclohexylmethoxy) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (247mg) and (4-methylbenzene) sulfonamide (148mg), colorless crystals of 3- (2-chloro-4- (cyclohexylmethoxy) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (252mg) were obtained. ¹H-NMR(CDCl₃): 0.98-1.87(11H, M), 2.42(3H, s), 2.62(3H, s), 2.66(3H, s), 3.74(2H, d, J ═ 7Hz), 5.49(2H, s), 6.71(2H, brs), 7.00(1H, d, J ═ 1Hz), 7.33(2H, d, J ═ 8Hz), 7.88(1H, s), 8.03(2H, d, J ═ 8Hz) masks (esi) M/z 579(M-1) example 228 (esi)

According to the same manner as in example 1, from 3- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (190mg) and 1-pentanesulfonamide (125mg), colorless crystals of 3- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (178mg) were obtained.¹H-NMR(CDCl₃): 0.88(3H, t, J ═ 7Hz), 1.22(3H, t, J ═ 7Hz), 1.28-1.48(4H, m), 1.88-1.93(2H, m), 2.62(3H, s), 2.62(2H, q, J ═ 7Hz), 2.74(3H, s), 3.52-3.57(2H, m), 5.52(2H, s), 6.60(1H, d, J ═ 8Hz), 7.00(1H, d, J ═ 8Hz), 7.31(1H, s), 8.01(1H, s) example 229

According to the same manner as in example 1, from 3- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (190mg) and (4-methylbenzene) sulfonamide (142mg), colorless crystals of 3- (2-chloro-4-ethylbenzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (173mg) were obtained. ¹H-NMR(CDCl₃)：1.24(3H，t，J＝7Hz)，2.42(3H，s)，2.61(3H，s)，2.64(2H，q，J＝7Hz)，2.68(3H，s)，5.53(2H，s)，6.61(1H，d，J＝8Hz)，7.01(1H，d，J＝8Hz)，7.30-7.34(3H，m), 7.90(1H, s), 8.04(2H, d, J ═ 8Hz) example 230

According to the same manner as in example 1, from 3- (2-chloro-4- (trifluoromethyl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (248mg) and 1-pentanesulfonamide (135mg), colorless crystals of 3- (2-chloro-4- (trifluoromethyl) benzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (210mg) were obtained.¹H-NMR(CDCl₃): 0.88(3H, t, J ═ 8Hz), 1.25-1.48(4H, m), 1.80-1.94(2H, m), 2.61(3H, s), 2.76(3H, s), 3.50-3.58(2H, m), 5.60(2H, s), 6.72(1H, d, J ═ 8Hz), 7.44(1H, brd, J ═ 8Hz), 7.77(1H, brs), 8.05(1H, s), 9.78(1H, brs) example 231

According to the same manner as in example 1, from 3- (2-chloro-4- (trifluoromethyl) benzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (238mg) and (4-methylbenzene) sulfonamide (159mg), colorless crystals of 3- (2-chloro-4- (trifluoromethyl) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (178mg) were obtained.¹H-NMR(CDCl₃): 2.42(3H, s), 2.60(3H, s), 2.69(3H, s), 5.61(2H, s), 6.73(1H, d, J ═ 8Hz), 7.33(2H, d, J ═ 8Hz), 7.44(1H, brd, J ═ 8Hz), 7.78(1H, brs), 7.93(1H, s), 8.02(1H, s), 10.05(1H, brs) example 232

According to the same manner as in example 1, from 3- (2-chloro-4-ethoxybenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (260mg) and 1-pentanesulfonamide (164mg), colorless crystals of 3- (2-chloro-4-ethoxybenzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine were obtained.¹H-NMR(CDCl₃): 0.89(3H, t, J ═ 7Hz), 1.26-1.51(7H, m), 1.80-1.94(2H, m), 2.64(3H, s), 2.73(3H, s), 3.52-3.57(2H, m), 4.01(2H, q, J ═ 7Hz), 5.49(2H, s), 6.72(2H, s), 6.99(1H, s), 7.99(1H, s), 9.89(1H, brs) example 233

By the same method as in example 1, from 3- (2-chloro-4-)Ethoxybenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (250mg) and (4-methylbenzene) sulfonamide (178mg) gave 3- (2-chloro-4-ethoxybenzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine as colorless crystals.¹H-NMR(CDCl₃): 1.42(3H, t, J ═ 7Hz), 2.42(3H, s), 2.62(3H, s), 2.66(3H, s), 4.03(2H, q, J ═ 7Hz), 5.49(2H, s), 6.72(1H, d, J ═ 8Hz), 6.77(1H, d, J ═ 8Hz), 7.01(1H, d, J ═ 1Hz), 7.33(2H, d, J ═ 8Hz), 7.88(1H, s), 8.03(2H, d, J ═ 8Hz), 10.14(1H, brs) example 234

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (300mg), N' -carbonyldiimidazole (218mg), DBU (0.20ml) and (4-methylbenzene) sulfonamide (230mg), 3- (2, 4-dichlorobenzyl) -2-methyl-5- (p-toluenesulfonylcarbamoyl) benzo [ b ] furan (90mg) was obtained as white crystals.¹H-NMR(DMSO-d₆，δppm)：2.37(3H，s)，4.06(2H，s)，7.16(1H，d，J＝8.4Hz)，7.32(1H，dd，J＝8.2 and 2.0Hz)，7.38(2H，d，J＝8.0Hz)，7.54(1H，d，J＝8.7Hz)，7.62(1H，d，J＝1.9Hz)，7.75(1H，d，J＝8.9Hz)，7.83(2H，d，J＝8.2Hz)，7.90(1H，s)，12.35(1H，brs)IR(Nujol)：1700cm^-1mp: example 235 at 121 ℃ of 120-

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (280mg), N' -carbonyldiimidazole (190mg), DBU (0.18ml) and (5-bromothien-2-yl) sulfonamide (280mg), white crystalline 5- ((5-bromothien-2-yl) sulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (350mg) was obtained.¹H-NMR(DMSO-d₆，δppm)：2.40(3H，s)，4.08(2H，s)，7.17(1H，d，J＝8.4Hz)，7.33(1H，dd，J＝8.4 and 2.2Hz)，7.35(1H，d，J＝4.1Hz)，7.58(1H，d，J＝8.7Hz)，7.63(1H，d，J＝2.1Hz)，7.64(1H，d，J＝4.0Hz)，7.79(1H，d，J＝8.7Hz)，7.96(1H，s)IR(Nujol)：1699cm^-1mp: 165-

According to the same manner as in example 1, from 5-carboxy-3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (230mg), N' -carbonyldiimidazole (170mg), DBU (0.16ml) and (5-chlorothien-2-yl) sulfonamide (210mg), white crystalline 5- ((5-chlorothien-2-yl) sulfonylcarbamoyl) -3- (2, 4-dichlorobenzyl) -2-methylbenzo [ b ] furan (210mg) was obtained.¹H-NMR(DMSO-d₆，δppm)：2.40(3H，s)，4.07(2H，s)，7.16(1H，d，J＝8.4Hz)，7.20(1H，d，J＝4.0)，7.32(1H，dd，J＝8.3 and 2.3Hz)，7.55(1H，d，J＝8.6Hz)，7.60-7.64(2H，m)，7.81(1H，dd，J＝8.7 and 1.8Hz)，7.94(1H，d，J＝1.5Hz)IR(Nujol)：1700cm^-1mp: 181 ℃ and 183 ℃ example 237

According to the same manner as in example 1, from 3- (2-chloro-4-phenylbenzyl) -2-methyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (150mg), N' -carbonyldiimidazole (84mg), DBU (79mg) and 4-pentene-1-sulfonamide (77mg), white crystalline 3- (2-chloro-4-phenylbenzyl) -2-methyl-5- ((4-pentene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (91mg) was obtained.¹H-NMR(DMSO-d₆δ ppm): 1.75-1.83(2H, m).2.10-2.16(2H, m), 2.49(3H, s), 3.52(2H, t, J ═ 7.7Hz), 4.94(1H, d, J ═ 11.3Hz), 4.98(1H, dd, J ═ 17.1 and2.6Hz), 5.70-5.76(1H, m), 5.86(2H, s), 6.89(1H, d, J ═ 8.1Hz), 7.38(1H, t, J ═ 7.3Hz), 7.45(2H, t, J ═ 7.3Hz), 7.54(1H, dd, J ═ 8.1 and 1.7Hz), 7.66(2H, d, J ═ 7.4), 7.84(1H, 84, J ═ 8H, 8.01, 8H, 8.8H, 8.7H, 8H: 152 ℃ and 155 ℃ example 238

According to the same manner as in example 1, from 6-carboxy-2- (2-chloro-4-phenylbenzyl) -3-methyl-2H-indazole (1.131g), N' -carbonyldiimidazole (0.63g), DBU (0.58m1) and p-toluenesulfonamide (0.67g), white crystalline 2- (2-chloro-4-phenylbenzyl) -3-methyl-6- (p-toluenesulfonylcarbamoyl) -2H-indazole (1.00g) was obtained. ¹H-NMR(DMSO-d₆，δppm)：2.39(3H，s)，2.65(3H，s)，5.77(2H，s)，6.80(1H，d，J ═ 8.1Hz), 7.34-7.47(6H, m), 7.56(1H, d, J ═ 8.2Hz), 7.66(2H, d, J ═ 7.8Hz), 7.78-7.81(2H, m), 7.89(2H, d, J ═ 8.2Hz), 8.22(1H, s), 12.42(1H, brs) mp: example 239 at 236-

3- (2-chloro-4- (1-hexynyl) benzyl) -2-methyl-5- (N- (4-methylbenzenesulfonyl) carbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (240mg) was catalytically reduced in dioxane using platinum oxide as a catalyst to give 3- (2-chloro-4-hexylbenzyl) -2-methyl-5- (N- (4-methylbenzenesulfonyl) carbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (181mg) as a colorless crystal.¹H-NMR(CDCl₃): 0.88(3H, t, J ═ 6Hz), 1.22-1.66(8H), 2.43(3H, s), 2.59(2H, t, J ═ 6Hz), 2.62(3H, s), 5.55(2H, s), 6.65(1H, d, J ═ 8Hz), 7.02(1H, d, J ═ 8Hz), 7.28-7.37(3H), 8.01-8.11(4H) mp: example 240 at 162-

To a toluene solution (5ml) of 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (500mg) was added sodium tert-butoxide (123mg), piperidine (109mg), (R) - (+) -BINAP (8mg), and tris (dibenzylideneacetone) -dipalladium (0) (4mg) in this order under a nitrogen atmosphere, and stirred at 90 ℃ for 30 hours. The reaction mixture was concentrated under reduced pressure, and water was added. 1N hydrochloric acid was added to bring the pH to 7, and extraction was carried out with chloroform/methanol at 4: 1. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Adding ethanol into the residue, heating, cooling, filtering, and collecting precipitated crystal. Dissolved in N, N-dimethylformamide (12ml) and hot water (8.5ml) was slowly added over an oil bath at 80 ℃. Cooling while stirring, filtering and collecting separated crystal. The crystals were washed with water and dried under reduced pressure with heating to give pale pink crystals of 3- (2-chloro-4-piperidinobenzylmethyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (391 mg). ¹H-NMR(CDCl₃)：1.65-1.70(6H，m)，2.42(3H，s)，2.64(3H，s)，2.65(3H，s)，3.19(4H，t，J＝7Hz)，5.45(2H，s)，6.75(2H，s)，6.95(1H，s)，7.32(2H，d，J＝8Hz)，7.86(1H，s)，8.04(2H，d，J＝8Hz)，10.18(1H，s)Mass(ESI)：m/z 550(M-H)^-mp: 190 ℃ and 192 ℃ example 241

According to the same manner as in example 240, from 3- (4-bromo-2-chlorobenzyl) -2, 7-dimethyl-5- ((4-methylbenzyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (500mg) and morpholine (191mg), colorless crystals of 3- (2-chloro-4-morpholinobenzyl) -2, 7-dimethyl-5- ((4-methylbenzyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (78mg) were obtained.¹H-NMR(CDCl₃)：2.42(3H，s)，2.65(3H，s)，2.66(3H，s)，3.18(4H，t，J＝7Hz)，3.85(4H，t，J＝7Hz)，5.46(2H，s)，6.73-6.82(2H，m)，6.95(1H，d，J＝2Hz)，7.33(2H，d，J＝8Hz)，7.86(1H，s)，8.05(2H，d，J＝8Hz)，10.14(1H，s)Mass(ESI)：m/z 552(M-H)^-mp: example 242 at 235-

According to the same manner as in example 240, from 3- (4-bromo-2-chlorophenylmethyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (600mg) and hexamethyleneimine (206mg), colorless crystals of 3- (2-chloro-4- (hexamethyleneimino) benzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (142mg) were obtained.¹H-NMR(CDCl₃)：1.50-1.60(4H，m)，1.80(4H，br)，2.42(3H，s)，2.65(3H，s)，2.66(3H，s)，3.43(4H，t，J＝7Hz)，5.44(2H，s)，6.53(1H，dd，J＝8，2Hz)，6.70(1H，d，J＝2Hz)，6.76(1H，d，J＝8Hz)，7.32(2H，d，J＝8Hz)，7.85(1H，s)，8.04(2H，d，J＝8Hz)Mass(ESI)：m/z 564(M-H)^-mp: 210 ℃ and 212 ℃ example 243

According to the same manner as in example 240, from 3- (4-bromo-2-chlorobenzyl) -2, 7-dimethyl-5- ((4-methylbenzyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (600mg) and pyrrolidine (148mg), colorless crystals of 3- (2-chloro-4- (1-pyrrolidinyl) benzyl) -2, 7-dimethyl-5- ((4-methylbenzyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (195mg) were obtained. ¹H-NMR(CDCl₃)：1.98-2.04(4H，m)，2.42(3H，s)，2.65(3H，s)，2.66(3H，s)，3.27(4H，t，J＝7Hz)，5.45(2H，s)，6.43(1H，dd，J＝8.2Hz)，6.59(1H，d，J＝2Hz)，6.83(1H，d，J＝8Hz)，7.32(2H，d，J＝8Hz)，7.84(1H，s)，8.03(2H，d，J＝8Hz)，10.21(1H，s)Mass(ESI)：m/z 536(M-H)^-mp: 212 ℃ 214 ℃ example 244

According to the same manner as in example 240, from 3- (4-bromo-2-chlorobenzyl) -2, 7-dimethyl-5- ((4-methylbenzyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (600mg) and 1-methylpiperazine (154mg), colorless crystals of 3- (2-chloro-4- (4-methylpiperazin-1-yl) benzyl) -2, 7-dimethyl-5- ((4-methylbenzyl) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (411mg) were obtained.¹H-NMR(CDCl₃)：2.35(3H，s)，2.42(3H，s)，2.55(4H，t，J＝7Hz)，2.64(3H，s)，2.65(3H，s)，3.24(4H，t，J＝7Hz)，5.46(2H，s)，6.77(2H，s)，6.96(1H，s)，7.33(2H，d，J＝8Hz)，7.86(1H，s)，8.03(2H，d，J＝8Hz)Mass(ESI)：m/z 568(M+H)⁺mp: example 245 at 149-

According to the same manner as in example 1, from 3- (2-chloro-4-methylthiobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (250mg) and (4-methylbenzene) sulfonamide (356mg), colorless crystals of 3- (2-chloro-4-methylthiobenzyl) -2, 7-dimethyl-5- ((4-methylbenzene) sulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (234mg) were obtained.¹H-NMR(CDCl₃): 2.42(3H, s), 2.50(3H, s), 2.62(3H, s), 2.67(3H, s), 5.51(2H, s), 6.69(1H, d, J ═ 8Hz), 7.08(1H, dd, J ═ 1, 8Hz), 7.32-7.35(3H, m), 7.88(1H, s), 8.04(2H, d, J ═ 8Hz) example 246

According to the same manner as in example 1, from 3- (2-chloro-4-methylthiobenzyl) -2, 7-dimethyl-3H-imidazo [ 4, 5-b ] pyridine-5-carboxylic acid (260mg) and 1-pentanesulfonamide (326mg), colorless crystals of 3- (2-chloro-4-methylthiobenzyl) -2, 7-dimethyl-5- (1-pentanesulfonylcarbamoyl) -3H-imidazo [ 4, 5-b ] pyridine (188mg) were obtained. ¹H-NMR(CDCl₃)：0.88(3H，t，J＝7Hz)，1.28-1.48(4H, m), 1.83-1.93(2H, m), 2.48(3H, s), 2.63(3H, s), 2.74(3H, s), 3.55(2H, m), 5.51(2H, s), 6.66(1H, d, J ═ 8Hz), 7.03(1H, dd, J ═ 1.8Hz), 7.31(1H, d, J ═ 1Hz), 8.00(1H, s) industrial applicability

The above-mentioned sulfonamide compound of the present invention and a pharmaceutically acceptable salt thereof are useful as a compound for preventing or treating glucose disorders, diabetes (type II diabetes, etc.), diabetic complications (e.g., diabetic gangrene, diabetic arthropathy, diabetic bone resorption, diabetic glomerulosclerosis, diabetic nephropathy, diabetic skin disorders, diabetic neuropathy, diabetic cataract, diabetic retinopathy, etc.), insulin resistance syndrome (insulin receptor abnormality, Rabson-Mendenhall syndrome, leprechaunism syndrome, Kobberlig-Dunnigan syndrome, Seip syndrome, Lawrence syndrome, Cushing syndrome, acromegaly, polycystic ovary syndrome, hyperlipidemia, atherosclerosis, cardiovascular diseases (angina pectoris, heart failure, etc.), hyperglycemia (e.g., hyperglycemia characterized by abnormal sugar metabolism such as eating disorder), etc., based on hypoglycemic activity, Or hypertension; and a drug based on cGMP-PDE (particularly PDE-V) inhibitory action, smooth muscle relaxation action, bronchodilator action, vasodilator action, smooth muscle cell inhibitory action, allergy inhibitory action, as a drug for treating angina pectoris, hypertension, pulmonary hypertension, blood stasis type heart failure, glomerular diseases (for example, diabetic glomerulosclerosis, etc.), tubulointerstitial diseases (for example, kidney diseases induced by FK506, cyclosporin, etc.), renal failure, atherosclerosis, angiostenosis (for example, angiostenosis after percutaneous arterioplasty), peripheral vascular diseases, stroke, chronic reversible occlusive diseases (for example, bronchitis, asthma (chronic asthma, allergic asthma)), autoimmune diseases, allergic rhinitis, urticaria, glaucoma, diseases characterized by intestinal motility disorder (for example, allergic intestinal syndrome), Pharmaceutical preparations useful for treating impotence (e.g., organic impotence, psychogenic impotence, etc.), nephritis, malignant disease or restenosis after PTCA, pancreatitis, or malignant disease (e.g., progressive weight loss such as lipolysis, muscular degeneration, anemia, edema, anorexia, etc., in chronic diseases such as cancer, tuberculosis, endocrine disorders, aids, etc.).

This application is based on Japanese application laid-open No. 208295 for special application No. 9 and laid-open No. 114718 for 10 years, and the contents thereof are also included in the scope of this specification.

Claims (14)

1. A sulfonamide compound represented by the general formula (I) or a salt thereof,

R¹-SO₂NHCO-A-X-R² (I)

(in the formula, R¹Represents an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, a cyclo-lower alkyl group which may be substituted, an aryl group which may be substituted or a heterocyclic group which may be substituted;

a represents a polycyclic heterocycle which may be substituted other than benzimidazolyl, indolyl, 4, 7-dihydrobenzimidazolyl and 2, 3-dihydrobenzoxazinyl;

x represents an alkylene group, an oxo group, an oxa lower alkylene group, a lower alkyleneoxo group, a carbonyl group, a lower alkenylene group, an imino group which may be substituted, an imino lower alkylene group which may be substituted, a lower alkyleneimino group which may be substituted, a thia lower alkylene group or a lower alkylenethia group;

R²represents an aryl group which may be substituted, a heterocyclic group which may be substituted or a substituted biphenyl group;

wherein, when A represents a 3H-imidazo [ 4, 5-b ] pyridyl group substituted with a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a biphenyl group substituted with a group other than tetrazolyl;

when A represents a quinolyl group substituted by a lower alkyl group, R²Represents an optionally substituted aryl group; a heterocyclic group which may be substituted; or biphenyl substituted with at least 1 substituent selected from the group consisting of alkyl, cyclo-lower alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocyclic lower alkyl other than tetrazolylmethyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carbamoyl, mono-lower alkylcarbamoyl, di-lower alkylcarbamoyl, nitro, halo-lower alkyl, aryl-lower alkenyl, aryl-lower alkoxy, lower alkoxy substituted with substituted amino, cyclo-lower alkyl-lower alkoxy, cyclo-lower alkyl, aryloxy-lower alkyl, acyloxy-lower alkyl, hydroxy-lower alkyl, mono-or di-lower alkylamino-lower alkyl, aryl-lower alkoxy-lower alkyl, arylthio-lower alkyl, cyano, carbamoyl, mono-lower alkylcarbamoyl, di-lower alkylcarbamoyl, nitro, halo-lower alkyl, aryl-lower alkoxy, heterocyclic lower alkoxy, heterocyclic oxygen lower alkyl, aryl lower alkylthio, aryl ureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted).

2. The sulfonamide compound or salt thereof according to claim 1, R¹Represents an optionally substituted alkyl group, an optionally substituted alkyl groupSubstituted alkenyl, alkynyl which may be substituted, cyclo-lower alkyl which may be substituted, aryl which may be substituted or heterocyclic group which may be substituted,

the substituents for substituting these groups are each independently selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkoxy, aryl, heterocyclo-loweralkyl, halogen, amino, substituted amino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carboxy, protected carboxy, carbamoyl, loweralkylcarbamoyl, nitro, halo-loweralkyl, arylloweralkyl, arylloweralkenyl, arylloweralkoxy, loweralkoxy substituted with substituted amino, cycloloweralkylloweralkoxy, cycloloweralkylloweralkyl, aryloxygrouralkyl, acyloxyaralkyl, hydroxyloweralkyl, mono-or di-loweralkylaminoloweralkyl, arylloweralkyloxyalkyl, arylthio-loweralkyl, heterocyclo-loweralkoxy, heterocyclic-loweralkyl, heterocyclic-substituted-, At least 1 of heteroepoxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

A represents a polycyclic heterocyclic group containing at least 1 hetero atom including an oxygen atom, a sulfur atom, a selenium atom and a nitrogen atom in addition to the benzimidazolyl group, the indolyl group, the 4, 7-dihydrobenzimidazolyl group and the 2, 3-dihydrobenzoxazinyl group, which may be substituted with at least 1 selected from the group consisting of alkyl, oxygen, sulfur, halogen, lower alkoxy, lower alkylthio, cyclo-lower alkyl, amino which may be substituted, aryl, heterocyclic group, lower alkylsulfonyl and lower alkylsulfinyl,

R²represents an aryl group which may be substituted, a heterocyclic group which may be substituted or a biphenyl group which may be substituted,

the substituents when these groups are substituted are independently selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkoxy, aryl, heterocyclo-loweralkyl, halogen, amino, substituted amino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carboxy, protected carboxy, carbamoyl, loweralkylcarbamoyl, nitro, halo-loweralkyl, arylloweralkyl, arylloweralkenyl, arylloweralkoxy, loweralkoxy substituted with substituted amino, cycloloweralkylloweralkoxy, cycloloweralkyl, aryloxygralkyl, acyloxyloweralkyl, hydroxyloweralkyl, mono-or di-loweralkylaminoloweralkyl, arylloweralkyloxyalkyl, arylthio-loweralkyl, heterocyclo-loweralkoxy, heterocyclic-loweralkoxy, and the like, At least 1 of heteroepoxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

Wherein, when A represents a 3H-imidazo [ 4, 5-b ] pyridyl group substituted with a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a biphenyl group substituted with a group other than tetrazolyl;

when A represents a quinolyl group substituted by a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a substituted biphenyl group,

the substituent when the above-mentioned aryl and heterocyclic groups are substituted is selected from the group consisting of alkyl, cyclo-lower alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocyclo-lower alkyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono-lower alkylcarbamoyl, di-lower alkylcarbamoyl, nitro, halogeno-lower alkyl, aryl-lower alkenyl, aryl-lower alkoxy, lower alkoxy substituted with substituted amino, cyclo-lower alkyl-lower alkoxy, cyclo-lower alkyl, aryloxy-lower alkyl, acyloxy-lower alkyl, hydroxy-lower alkyl, mono-or di-lower alkylamino-lower alkyl, aryl-lower alkoxy-lower alkyl, arylthio-lower alkyl, heterocyclo-lower alkoxy, heterocyclic-lower alkoxy, heterocyclic-lower alkyl, heterocyclic-substituted aryl, heterocyclic group, and the like, At least 1 of heteroepoxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

The substituent for the above-mentioned biphenyl group is selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkoxy, phenyl, heterocyclo-loweralkyl other than tetrazolylmethyl, halogen, amino, substituted amino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carbamoyl, loweralalkylcarbamoyl, loweralkylcarbamoyl, nitro, halogeno-loweralkyl, aryl-loweralkenyl, aryl-loweralkoxy, loweralkoxy substituted with substituted amino, cycloloweralkylloweralkoxy, cycloloweralkyl, aryloxygienyl-loweralkyl, hydroxy-loweralkyl, mono-or di-loweralkylamino-loweralkyl, arylloweralkyl, arylthioloweralkyl, heterocyclo-loweralkoxy, heterocyclo-loweralkyl, at least 1 of aryl lower alkylthio, aryl ureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted.

3. The sulfonamide compound or salt thereof according to claim 2, R ¹Represents an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, a cyclo-lower alkyl group which may be substituted, a phenyl group which may be substituted or a heterocyclic group which may be substituted,

the substituents when these groups are substituted are each independently selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkoxy, phenyl, heterocyclo-loweralkyl, halogen, amino, loweralkylacylamino, mono-loweralkylamino, di-loweralkylamino, N-loweralkyl-N-acylamino, loweralkylsulfonylamino, aryl-loweralkylamino, N-heterocyclyl-N-loweralkylamino, arylsulfonylamino, arylcarbonylamino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carboxy, protected carboxy, carbamoyl, mono-loweralalkylcarbamoyl, di-loweralkylcarbamoyl, nitro, halo-loweralkyl, arylloweralkyl, arylloweralkenyl, arylloweralkoxy, loweralkylacylamino-loweralkoxy, lower alkanoylamino-alkoxyl, lower alkoxyl, At least 1 member selected from the group consisting of mono-lower alkylamino lower alkoxy, di-lower alkylamino lower alkoxy, N-lower alkyl-N-acylamino lower alkoxy, lower alkylsulfonylamino lower alkoxy, aryl lower alkylamino lower alkoxy, N-heterocycle-N-lower alkylamino lower alkoxy, arylsulfonylamino lower alkoxy, arylcarbonylamino lower alkoxy, cyclo-lower alkyl, aryloxo lower alkyl, acyloxylower alkyl, hydroxylower alkyl, mono-or di-lower alkylamino lower alkyl, aryl lower alkoxy lower alkyl, arylthio lower alkyl, heterocycle lower alkoxy, heterocyclyloxylower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted,

A represents a bicyclic heterocyclic group represented by the following (A) to (I) which may be substituted with at least 1 member selected from the group consisting of alkyl, oxygen, sulfur, halogen, lower alkoxy, lower alkylthio, cyclo-lower alkyl, amino, lower alkanoylamino, mono-lower alkylamino, di-lower alkylamino, N-lower alkyl-N-acylamino, lower alkylsulfonylamino, aryl-lower alkylamino, N-heterocycle-N-lower alkylamino, arylsulfonylamino, arylcarbonylamino, aryl, heterocyclic group, lower alkylsulfonyl and lower alkylsulfinyl, in addition to benzimidazolyl, indolyl, 4, 7-dihydrobenzimidazolyl and 2, 3-dihydrobenzoxazinyl,

wherein, when A represents a 3H-imidazo [ 4, 5-b ] pyridyl group substituted with a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a biphenyl group substituted with a group other than tetrazolyl;

when A represents a quinolyl group substituted by a lower alkyl group, R²Represents an optionally substituted phenyl groupA substituted naphthyl group, a heterocyclic group which may be substituted, or a substituted biphenyl group,

the substituent for substituting the above-mentioned phenyl, naphthyl and heterocyclic groups is selected from the group consisting of alkyl, cyclo-lower alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocyclic lower alkyl, halogen, amino, lower alkanoylamino, mono-lower alkylamino, di-lower alkylamino, N-lower alkyl-N-acylamino, lower alkylsulfonylamino, aryl-lower alkylamino, N-heterocyclic-N-lower alkylamino, arylsulfonylamino, arylcarbonylamino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxyl, protected carboxyl, carbamoyl, mono-lower alkylcarbamoyl, di-lower alkylcarbamoyl, nitro, halogeno-lower alkyl, aryl-lower alkenyl, aryl-lower alkoxy, lower alkanoylamino-lower alkoxy, lower alkoxyalkoxy, lower alkoxysulfonyl, lower alkoxy, At least 1 of mono-lower alkylamino lower alkoxy, di-lower alkylamino lower alkoxy, N-lower alkyl-N-acylamino lower alkoxy, lower alkylsulfonylamino lower alkoxy, aryl lower alkylamino lower alkoxy, N-heterocycle-N-lower alkylamino lower alkoxy, arylsulfonylamino lower alkoxy, arylcarbonylamino lower alkoxy, cyclo-lower alkyl, aryloxo lower alkyl, acyloxylower alkyl, hydroxylower alkyl, mono-or di-lower alkylamino lower alkyl, aryl lower alkoxy lower alkyl, arylthio lower alkyl, heterocycle lower alkoxy, heterocyclyloxylower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, alkyl substituted with a 2-valent heterocyclic group which may be substituted and a heterocyclic group which may be substituted,

The substituent for the above-mentioned biphenyl group is selected from the group consisting of alkyl, cycloloweralkyl, alkenyl, alkynyl, loweralkylacyl, loweralkyloxy, phenyl, heterocyclic loweralkyl other than tetrazolylmethyl, halogen, amino, loweralkylacylamino, loweralkylamino, N-loweralkyl-N-acylamino, loweralkylsulfonylamino, aryl loweralkylamino, N-heterocyclic-N-loweralkylamino, arylsulfonylamino, arylcarbonylamino, loweralkylsulfonyl, loweralkylsulfinyl, loweralkylthio, cyano, carbamoyl, loweralkylcarbamoyl, nitro, halogenated loweralkyl, aryl loweralkenyl, aryl loweralkoxy, loweralkylacylamino loweralkoxy, lower alkylthioalkoxy, lower alkylthionyl, aryl loweralkyl, at least 1 of mono-lower alkylamino lower alkoxy, di-lower alkylamino lower alkoxy, N-lower alkyl-N-acylamino lower alkoxy, lower alkylsulfonylamino lower alkoxy, aryl lower alkylamino lower alkoxy, N-heterocycle-N-lower alkylamino lower alkoxy, arylsulfonylamino lower alkoxy, arylcarbonylamino lower alkoxy, cyclo-lower alkyl, aryloxo lower alkyl, acyloxylower alkyl, hydroxylower alkyl, mono-or di-lower alkylamino lower alkyl, aryl lower alkoxy lower alkyl, arylthio lower alkyl, heterocycle lower alkoxy, heterocycloyloxy lower alkyl, aryl lower alkylthio, arylureido, lower alkoxy, aryl lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted and a heterocyclic group which may be substituted,

The heterocyclic group is a heterocyclic ring represented by the following (A) to (T),

(A) a saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 4 nitrogen atoms

(B) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 3 oxygen atoms

(C) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 3 sulfur atoms

(D) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 3 nitrogen atoms and 1 to 2 oxygen atoms

(E) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 3 nitrogen atoms and 1 to 2 sulfur atoms

(F) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 2 oxygen atoms and 1 to 2 sulfur atoms

(G) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 nitrogen atom, 1 oxygen atom and 1 sulfur atom

(H) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 2 selenium atoms

(I) A saturated or unsaturated 7-to 12-membered bicyclic heterocyclic group containing 1 to 2 selenium atoms and 1 to 3 nitrogen atoms

(J) Unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atoms

(K) Saturated 3-to 8-membered heteromonocyclic group containing 1 to 4 nitrogen atoms

(L) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms

(M) a saturated 3-to 8-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms

(N) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms

(O) a saturated 3-to 8-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms

(P) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 2 sulfur atoms

(Q) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 to 2 oxygen atoms

(R) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 oxygen atom

(S) spiroheterocyclic group containing 1 to 2 oxygen atoms

(T) an unsaturated 3-to 8-membered heteromonocyclic group containing 1 oxygen atom and 1-2 sulfur atoms.

4. The sulfonamide compound or the salt thereof according to claim 3, wherein A is a compound selected from the group consisting of 2, 3-dihydrobenzimidazolyl, pyrazolopyrimidyl, tetrahydropyrazolopyrimidyl, imidazopyrazolyl, dihydroimidazopyrazolyl, imidazopyridyl, pyrrolopyridinyl, pyrazolopyridyl, benzopyrazolyl, dihydrobenzimidazolyl, benzotriazolyl, indolizinyl, isoindolyl, indazolyl, indolinyl, isoindolinyl, purinyl, quinolizinyl, quinolyl, phthalazinyl, naphthylamino, quinoxalyl, dihydroquinoxalyl, tetrahydroquinoxalyl, quinazolinyl, dihydroquinazolinyl, tetrahydroquinazolinyl, cinnolinyl, pteridinyl, pyrazinopyridazinyl, imidazotriazinyl, imidazopyrazinyl, imidazopyrimidinyl, imidazopyridazinyl, 1H-1- (or 2) indolinyl, Benzofuranyl, isobenzofuranyl, furopyridinyl, benzopyranyl, chromanyl, isobenzodihydropyranyl, benzoxepin-trienyl, cyclopentapyranyl, furopyranyl, benzothienyl, dihydrodithianyl, dithianyl, dioxolyl, benzoxazinyl, pyridooxazinyl, pyrazolooxazinyl, furopyridinyl, thienoimidazolyl, thienopyridinyl, dithiadiazahydroindenyl, thienofuranyl, oxathiolanylcyclopentazolyl (oxathiolaphthyryl), benzoselenophenyl, selenophenopyridinyl, benzoselenophenediazolyl (benzoselenol), selenophenopyridinyl, and cyclopentopyridyl, and these heterocyclic groups may also be substituted with at least 1 selected from alkyl and oxygen.

5. The sulfonamide compound or salt thereof according to claim 4, wherein R is¹Represents alkyl, alkenyl, phenyl lower alkenyl, nitro, phenyl which may be substituted by a substituent selected from alkyl and alkenyl, thienyl which may be substituted by halogen; or a quinolyl group, or a salt thereof,

a is a heterocyclic group selected from the group consisting of 2, 3-dihydrobenzimidazolyl, imidazopyrazolyl, imidazopyridinyl, pyrrolopyridinyl, pyrazolopyridinyl, benzotriazolyl, indolizinyl, indazolyl, quinolinyl, dihydroquinoxalinyl, tetrahydroquinoxalinyl, dihydroquinazolinyl, tetrahydroquinazolinyl, benzofuranyl, benzothienyl and thienoimidazolyl, and these heterocyclic groups may also be substituted by alkyl and/or oxygen,

x is lower alkylene, oxa lower alkylene or oxygen,

R²is alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, imidazolyl lower alkyl, piperidinyl lower alkyl, halogen, amino, lower alkanoylamino, mono-lower alkylamino, di-lower alkylamino, N-lower alkyl-N-lower alkanoylamino, N-lower alkanoylaminoalkyl-N-benzoylamino, lower alkylsulfonylamino, phenyl lower alkylamino, phenylsulfonylamino, benzoylamino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkylthio, cyano, carboxy, lower alkoxycarbonyl, cyclo lower alkyloxycarbonyl, mono lower alkylcarbamoyl, nitro, halo lower alkyl, phenyl lower alkenyl, phenyl lower alkoxy, (N-pyridyl-N-lower alkylamino) lower alkoxy, cyclo lower alkyl, phenoxy lower alkyl, lower alkylsulfonyloxy lower alkyl, hydroxy lower alkyl, di lower alkylamino lower alkyl, phenyl lower alkoxy lower alkyl, phenylthio lower alkyl, thienyl lower alkoxy, pyridyloxy lower alkyl, phenylthio lower alkoxy, phenylthio lower alkyl, amino lower alkyl, phenylthio lower alkyl, amino, nitro, lower alkyl, alkoxy, lower alkyl, nitro, lower alkyl, phenyl lower alkylthio, phenylureido, lower alkoxy, phenyl lower alkynyl, dioxothiazolidinylidene lower alkyl, phenyl which may be substituted (the substituent is selected from the group consisting of thienyl which may be substituted by halogen), naphthyl which may be substituted by halogen, 4-phenylphenyl which may be substituted by halogen, thienyl which may be substituted by halogen, benzothienyl which may be substituted by halogen, quinolyl which may be substituted by halogen, or benzotetrahydrofuryl which may be substituted by halogen.

6. The sulfonamide compound or salt thereof according to claim 5, wherein R is¹Represents alkyl, alkenyl, phenyl lower alkenyl, phenyl which may be substituted by a substituent selected from the group consisting of alkyl and alkenyl, thienyl which may be substituted by halogen,

a is a heterocyclic group selected from the group consisting of 3H-imidazo [ 4, 5-b ] pyridyl, pyrazolo [ 1, 5-a ] pyridyl, indolizinyl, 1H-indazolyl, benzo [ b ] furyl and benzo [ b ] thienyl, and these heterocyclic groups may also be substituted by 1 to 2 alkyl groups,

x is a lower alkylene group,

R²is alkyl, alkenyl, alkynyl, lower alkoxy, phenyl, halogen, di-lower alkylamino, lower alkylthio, lower alkoxycarbonyl, nitro, halogenated lower alkyl, phenyl lower alkenylPhenyl lower alkoxy, cyclo lower alkyl lower alkoxy, phenoxy lower alkyl, phenyl lower alkoxy lower alkyl, phenyl lower alkynyl and phenyl which may be substituted (the substituents are selected from thienyl which may be substituted by halogen), naphthyl which may be substituted by halogen or 4-phenylphenyl which may be substituted by halogen.

7. A sulfonamide compound or a salt thereof according to claim 6, wherein A is a 3H-imidazo [ 4, 5-b ] pyridyl, 1H-indazolyl or benzo [ b ] furyl group, each of which may be substituted by an alkyl group, and R is ²Is phenyl substituted by halogen, which phenyl may also be substituted by substituents selected from the group consisting of alkyl, alkenyl, alkynyl, lower alkoxy, phenyl, halogen, di-lower alkylamino, lower alkylthio, lower alkoxycarbonyl, nitro, halo-lower alkyl, phenyl-lower alkenyl, phenyl-lower alkoxy, cyclo-lower alkyl-lower alkoxy, phenoxy-lower alkyl, phenyl-lower alkoxy-lower alkyl, phenyl-lower alkynyl and thienyl which may be substituted by halogen, or R²Is naphthyl substituted by halogen.

8. A sulfonamide compound or a salt thereof according to claim 7, wherein A is a 3H-imidazo [ 4, 5-b ] pyridyl group substituted by 1 or 2 lower alkyl groups.

9. A sulfonamide compound or a salt thereof as claimed in claim 7, wherein A is 1H-indazolyl substituted with 1 lower alkyl group.

10. A sulfonamide compound or a salt thereof according to claim 7, wherein A is a benzo [ b ] furyl group substituted by 1 lower alkyl group.

11. General formula (I)

R¹-SO₂NHCO-A-X-R² (I)

(wherein each symbol is the same as above) or a salt thereof,

comprising reacting (1) a compound represented by the formula (II) or a salt thereof with a compound represented by the formula (III), a reactive derivative thereof at a carboxyl group or a salt thereof to produce a compound represented by the formula (I) or a salt thereof,

R¹-SO₂NH₂ (II)

(in the formula, R¹Represents an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, a cyclo-lower alkyl group which may be substituted, an aryl group which may be substituted or a heterocyclic group which may be substituted)

HOOC-A-X-R² (III)

(wherein A represents a polycyclic heterocycle which may be substituted other than benzimidazolyl, indolyl, 4, 7-dihydrobenzimidazolyl and 2, 3-dihydrobenzoxazinyl;

x represents an alkylene group, an oxo group, an oxa lower alkylene group, a lower alkyleneoxo group, a carbonyl group, a lower alkenylene group, an imino group which may be substituted, an imino lower alkylene group which may be substituted, a lower alkyleneimino group which may be substituted, a thia lower alkylene group or a lower alkylenethia group;

R²represents an aryl group which may be substituted, a heterocyclic group which may be substituted or a substituted biphenyl group;

wherein, when A represents a 3H-imidazo [ 4, 5-b ] pyridyl group substituted with a lower alkyl group, R²Represents an aryl group which may be substituted, a heterocyclic group which may be substituted, or a biphenyl group substituted with a group other than tetrazolyl;

when A represents a quinolyl group substituted by a lower alkyl group, R²Represents an optionally substituted aryl group; a heterocyclic group which may be substituted; or biphenyl substituted with at least 1 substituent selected from the group consisting of alkyl, cyclo-lower alkyl, alkenyl, alkynyl, lower alkanoyl, lower alkoxy, phenyl, heterocyclic lower alkyl other than tetrazolylmethyl, halogen, amino, substituted amino, lower alkylsulfonyl, lower alkylsulfinyl, lower alkanoylamino, lower alkoxycarbonyl Thio, cyano, carbamoyl, mono-lower alkylcarbamoyl, di-lower alkylcarbamoyl, nitro, halogeno-lower alkyl, aryl-lower alkenyl, aryl-lower alkoxy, lower alkoxy substituted with substituted amino, cyclo-lower alkyl-lower alkoxy, cyclo-lower alkyl, aryloxy-lower alkyl, acyloxy-lower alkyl, hydroxy-lower alkyl, mono-or di-lower alkylamino-lower alkyl, aryl-lower alkoxy-lower alkyl, arylthio-lower alkyl, heterocyclic-lower alkoxy, heterocyclic-oxy-lower alkyl, aryl-lower alkylthio, arylureido, lower alkoxy-lower alkoxy, aryl-lower alkynyl, lower alkyl substituted with a 2-valent heterocyclic group which may be substituted, and a heterocyclic group which may be substituted)

R¹-SO₂NHCO-A-X-R² (I)

(in the formula, each symbol is the same as above);

(2) preparing a compound represented by the formula (I-2) or a salt thereof by reducing a compound represented by the formula (I-1) or a salt thereof,

R¹-SO₂NHCO-A-X-R²⁰¹ (I-1)

(in the formula, R²⁰¹Is an optionally substituted aryl group, an optionally substituted heterocyclic group or an optionally substituted biphenyl group having at least an alkynyl group, an aryl lower alkenyl group, a terminal nitro group or a terminal formyl group, the other symbols being as defined above)

R¹-SO₂NHCO-A-X-R²⁰² (I-2)

(in the formula, R²⁰²An aryl group which may be substituted, a heterocyclic group which may be substituted or a substituted biphenyl group, which has at least an alkyl group, an aryl lower alkyl group, a terminal amino group or a hydroxymethyl group, and the other symbols are the same as those described above);

(3) by oxidizing a compound represented by the formula (I-3) or a salt thereof to obtain a compound represented by the formula (I-4) or a salt thereof,

R¹-SO₂NHCO-A-X-R²⁰³ (I-3)

(in the formula, R²⁰³An aryl group which may be substituted, a heterocyclic group which may be substituted or a substituted biphenyl group, which has at least a terminal formyl group and the other symbols are the same as those described above),

R¹-SO₂NHCO-A-X-R²⁰⁴ (I-4)

(in the formula, R²⁰⁴An aryl group which may be substituted, a heterocyclic group which may be substituted, or a substituted biphenyl group, these groups having at least a carboxyl group, the other symbols being the same as those described above);

(4) by acylating a compound represented by the formula (I-5) or a salt thereof to produce a compound represented by the formula (I-6) or a salt thereof,

R¹-SO₂NHCO-A-X-R²⁰⁵ (I-5)

(in the formula, R²⁰⁵Is an optionally substituted aryl group, an optionally substituted heterocyclic group or an optionally substituted biphenyl group, which has at least a hydroxy lower alkyl group and the other symbols are the same as those mentioned above)

R¹-SO₂NHCO-A-X-R²⁰⁶ (I-6)

(in the formula, R²⁰⁶An aryl group which may be substituted, a heterocyclic group which may be substituted or a substituted biphenyl group, these groups having at least an acyloxyloweralkyl group, the other symbols being the same as those described above);

(5) A compound represented by the formula (I-7) or a salt thereof is produced by aryloxylating a compound represented by the formula (I-6) or a salt thereof,

R¹-SO₂NHCO-A-X-R²⁰⁶ (I-6)

(in the formula, R²⁰⁶Is an optionally substituted aryl group, an optionally substituted heterocyclic group or an optionally substituted biphenyl group, which has at least an acyloxo lower alkyl group, the other symbols being as defined above)

R¹-SO₂NHCO-A-X-R²⁰⁷ (I-7)

(in the formula, R²⁰⁷An optionally substituted aryl group, an optionally substituted heterocyclic group or an optionally substituted biphenyl group, which has at least an aryloxycarbonyllower alkyl group and the other symbols are the same as those described above);

(6) the compound represented by the formula (I-8) or a salt thereof is produced by introducing a carboxyl-protecting group into the compound represented by the formula (I-4) or a reactive derivative thereof,

R¹-SO₂NHCO-A-X-R²⁰⁴ (I-4)

(wherein each symbol is the same as described above),

R¹-SO₂NHCO-A-X-R²⁰⁸ (I-8)

(in the formula, R²⁰⁸An aryl group which may be substituted, a heterocyclic group which may be substituted or a substituted biphenyl group, these groups having at least a protected carboxyl group);

(7) amidating a compound represented by the formula (I-4) or a reactive derivative thereof to produce a compound represented by the formula (I-9) or a salt thereof,

R¹-SO₂NHCO-A-X-R²⁰⁴ (I-4)

(wherein each symbol is the same as described above),

R¹-SO₂NHCO-A-X-R²⁰⁹ (I-9)

(in the formula, R²⁰⁹An aryl group which may be substituted, a heterocyclic group which may be substituted, or a substituted biphenyl group, these groups having at least an amide group which may be substituted, the others being the same as described above), or

(8) A compound represented by the formula (I-11) or a salt thereof is produced by adding a heterocyclic group containing nitrogen to a compound represented by the formula (I-10) or a salt thereof,

R¹-SO₂NHCO-A-X-R²¹⁰ (I-10)

(in the formula, R²¹⁰An optionally substituted aryl group having at least a halogen atom and the other symbols being the same as those described above),

R¹-SO₂NHCO-A-X-R²¹¹ (I-11)

(in the formula, R²¹¹A compound represented by the formula (I) wherein the aryl group which may be substituted is at least substituted by a nitrogen-containing heterocyclic group and the other symbols are the same as those in the above) or a salt thereof

R¹-SO₂NHCO-A-X-R² (I)

(wherein each symbol is the same as described above).

12. A pharmaceutical composition containing the sulfonamide compound or a pharmaceutically acceptable salt thereof according to claim 1.

13. A method for treating diseases which can be cured on the basis of hypoglycemic action and diseases which can be cured on the basis of cGMP-PDE inhibitory action, smooth muscle relaxing action, bronchodilatory action, vasodilatory action, smooth muscle cell inhibitory action or allergy inhibitory action, which comprises using a sulfonamide compound or a pharmaceutically acceptable salt thereof as claimed in claim 1.

14. Use of a sulfonamide compound or a pharmaceutically acceptable salt thereof according to claim 1 for the preparation of a therapeutic agent for diseases curable on the basis of hypoglycemic action and diseases curable on the basis of cGMP-PDE inhibitory action, smooth muscle relaxing action, bronchodilatory action, vasodilatory action, smooth muscle cell inhibitory action or allergy inhibitory action.