WO1997030030A1 - Indole derivatives - Google Patents

Abstract

Compounds represented by general formula (1) or hydrates thereof, which have a COX-2 inhibitory effect and are useful as drugs such as an antiinflammatory agent, wherein R1 represents linear or branched C¿1-7? alkyl, etc.; R?2¿ represents methanesulfonyl, etc.; and R3 represents optionally substituted phenyl, etc.

Description

 Indole derivative Technical field

 The present invention relates to a novel indole derivative which exhibits an anti-inflammatory effect and the like and is useful as a medicine. Background art

 Currently, most of the drugs widely used as anti-inflammatory drugs are nonsteroidal anti-inflammatory drugs whose mechanism of action is inhibition of cycling xygenase (COX), which is involved in the biosynthesis of prostaglandin E 2 (PG E 2). Agent (NSA ID). However, the synthetic activity of PGE2 is present in all tissues of the living body and controls the homeostasis of the living body, and when NSAID is administered thereto, various side effects are caused. For example, although PGE 2 has an effect of maintaining blood flow in these devices in the night kidney, administration of NSAIDs makes it difficult to maintain local blood flow, causing gastric and renal injury. Wake up.

 Under these circumstances, the existence of a COX isozyme was confirmed. In order to distinguish the name from the previously recognized COX, the conventional type was called COX-1 and the newly discovered isozyme was called COX-2. In addition, it was revealed that COX-2 is induced during inflammation and is rarely expressed normally, and it also becomes clear that the conventional NSAID nonspecifically inhibited both enzymes. Was. This raises the possibility that a compound having a COX-2 inhibitory effect may be a new anti-inflammatory agent.

At present, several compounds that do not inhibit COX-1 but selectively inhibit only COX-2 are known (inflammation and immunity, 3 (1), 29-36, 1995, Bioorganic & Me d.Chem.Let t.5 (8), 867-87 2, 199 5 etc.). However, none of these effects are satisfactory, and there is a need for a drug that exhibits better C0X-2 inhibitory activity.

 An object of the present invention is to provide an indole derivative having COX-2 inhibitory activity and the like, which is useful as a drug such as an anti-inflammatory agent.

 The present inventors have conducted intensive studies with the aim of developing compounds that selectively or non-selectively inhibit COX-2 and have anti-inflammatory effects equal to or higher than existing NSAIDs such as indomethacin. As a result, they have found that the indole derivative represented by the general formula (1) has excellent anti-inflammatory activity and is useful as a medicament, and based on this finding, completed the present invention. Disclosure of the invention

 That is, the present invention provides a compound represented by the general formula (1):

In the formula, R ¹ is a hydrogen atom, a linear or branched alkyl group having〗 7 carbon atoms, a linear or branched alkenyl group having 2 to 7 carbon atoms, A straight-chain or branched alkynyl group, a cycloalkenyl group having 4 to 6 carbon atoms, an aryl group, a heteroaryl group, or a linear or branched alkyl group having an alkyl moiety of 7 to 7 carbon atoms An alkylcarbonyl group, an alkenyl moiety wherein the alkenyl moiety is a straight-chain or branched alkenyl group having 2 to 7 carbon atoms, and an alkynyl moiety wherein the alkynyl moiety is a straight-chain or branched alkynyl having 2 to 7 carbon atoms. An alkynylcarbonyl group or one (CH ₂ ) _m —R ⁴

Here, m represents an integer of 0 to 3, and R ⁴ is a cycloalkyl having 3 to 6 carbon atoms which may be substituted with a linear or branched alkyl group having 1 to 3 carbon atoms. Represents the radical

R ² represents one S〇 ₂ —R ^s . Here, R ⁵ represents a linear or branched alkyl group having 1 to 3 carbon atoms.

R ³ is an aryl group which may have a substituent, a cycloalkyl group having 3 to 6 carbon atoms which may have a substituent, or a monocyclic hetero group which may have a substituent ¾ represents a group,

Or a hydrate thereof. BEST MODE FOR CARRYING OUT THE INVENTION

In the definition of the compound represented by the general formula (1), examples of the linear or branched alkyl group having 1 to 7 carbon atoms in R ¹ include a methyl group, an ethyl group, an n-propyl group, Propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, n-pentyl group, π-hexyl group, n- ^ butyl group and the like. Six straight-chain or branched alkyl groups are preferred, and a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentisole group, and an n-hexizole group are more preferred.

 Examples of the linear or branched alkenyl group having 2 to 7 carbon atoms for R ′ include, for example, a vinyl group, an aryl group, and an i-propenyl group. Alternatively, a branched alkenyl group is preferable, and an aryl group and an i-propenyl group are more preferable.

Examples of the linear or branched alkynyl group having 2 to 7 carbon atoms in R ¹ include an ethynyl group and the like, and a straight-chain or branched alkynyl group having 2 to 4 carbon atoms is preferred. preferable.

Examples of the cycloalkenyl group having 4 to 6 carbon atoms in R ¹ include a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group and the like, and a cyclohexenyl group is preferable.

The aryl group in R ¹ is a monocyclic, polycyclic, or fused polycyclic having 6 to 12 carbon atoms. And a phenyl group, a biphenyl group and the like, and a phenyl group is preferable.

 The heteroaryl group for R ′ is a 5- or 6-membered ring containing one or two hetero atoms such as nitrogen IS atoms as ring-constituting atoms, and examples thereof include a pyridyl group.

The alkylcarbonyl group in which the alkyl moiety in R ¹ is a linear or branched alkyl group having 1 to 7 carbon atoms refers to the above-described starved or branched alkyl group having 1 to 7 carbon atoms All alkyl carbonyl groups include, for example, acetyl group, propionyl group, butyryl group, 2-methylpropionyl group, etc., wherein the alkyl moiety is an aba-chain or branched-chain alkyl group having 1 to 4 carbon atoms. An alkylcarbonyl group is preferred.

An alkenylcarbonyl group in which the alkenyl moiety in R ¹ is a chain chain or branched alkenyl group having 2 to 7 carbon atoms refers to the above-mentioned straight or branched alkenyl group having 2 to 7 carbon atoms. All alkenyl carboxy groups, such as ぱ, acryloyl group, methacryloyl group, crotonyl group, 2,4-hexaenoyl group, etc., wherein the alkenyl moiety has 2 to 4 carbon atoms. Alkenylcarbonyl groups, which are branched alkenyl groups, are preferred.

 The alkynylcarbonyl group in which the alkynyl moiety in R ′ is a straight-chain or branched alkynyl group having 2 to 7 carbon atoms refers to the above-mentioned straight-chain or branched alkynyl group having 2 to 7 carbon atoms. And all alkynylcarbonyl groups such as a propioyl group. An alkynylcarbonyl group in which the alkynyl moiety is a straight-chain or branched alkynyl group having 2 to 4 carbon atoms is preferable.

The chain- or branched-chain alkyl group having 1 to 3 carbon atoms as a substituent in R ⁴ represents a methyl group, an ethyl group, a π-propyl group, or an i-propyl group.

Examples of the cycloalkyl group having 3 to 6 carbon atoms which may be substituted with a straight or branched alkyl group having 1 to 3 carbon atoms for R ⁴ include, for example, a cyclopropyl group, a methylcyclopropyl group , Ethylcyclopropyl, cyclobutyl, cyclo Examples thereof include a pentyl group and a cyclohexyl group, and a cyclopropyl group is preferable.

Examples of the group represented by 1 (CH ₂ ) _m —R ⁴ in R ′ include a cyclopropyl group, a methylcyclopropyl group, an ethylcyclopropyl group, a cyclopropylmethyl group, a cyclobutylpyruethyl group, and a 2-methyl group Cyclopropylmethyl, 2-methylcyclopropylethyl, 2-ethylcyclopropylmethyl, 2-ethylcyclopropylethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl, cyclo Examples include a hexyl group and a cyclohexylmethyl group, and a cyclopropylmethyl group is preferable.

 R ′ represents a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, an aryl group, a propenyl group, and a cyclohexene 1 Preferred are a methyl group, a cyclomethyl pyrmethyl group and a phenyl group.

One SO ₂ in R ² - groups represented by R ⁵ are methanesulfonyl group, Etansuru Honiru group, n- propanesulfonyl group, i indicates an propanesulfonyl two group, meta Nsuruhoniru group, ethanesulfonyl group, n- A propanesulfonyl group is preferred, and a methanesulfonyl group and an ethanesulfonyl group are more preferred.

An aryl group which may have a substituent in R ^3, a cycloalkyl group having 3 to 6 carbon atoms which may have a substituent, or a single rose type which may have a substituent Examples of the substituent of the ring group include a halogen atom, a linear or branched alkyl group or alkoxy group having 4 to 4 carbon atoms which may be substituted with a halogen atom, or one S (0) _n. -R ⁶ (where n represents an integer of 0 to 2, R ⁶ represents a linear or branched alkyl group having 1 to 3 carbon atoms), an amino group, a divalent group, etc. Fluorine atom, chlorine atom, iodine atom, iodine atom, methyl group, ethyl group, n-propyl group, i-propyl group, t-butyl group, trifluoromethyl group, methoxy group, ethoxy group, methylthio group , Methanesulfonyl group, ethanesulfonyl group, amino group, Nitro groups are preferred.

The aryl group which may have a substituent in R ³ is the same or different, In the above substituents, mono, di, tri may be an aryl group having 6 to 12 carbon atoms which may be substituted, and may be the same or different, and in the above B substituent, mono, di, tri An optionally substituted phenyl group is preferable, and a phenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-iodophenyl group, a 2,3-difluorophenyl group, a 2,3-difluorophenyl group, 4-dichlorophenyl group, 2,6-dichlorophenyl group, 3,4-dichlorophenyl group, 3,5-dichlorophenyl group, 3,5-dibromophenyl group, 5-bromo-2-chlorophenyl group, 2,3, 5-Trichloro mouth phenyl group, 2,4,6-trichlorophenyl group, 2-chloro-4,5-difluorophenyl group, 4-methylphenyl group, 4-ethylphenyl group, 4-n-propylphenyl group, 41T Sopropyl Hue 2-, 4-, 6-trimethylphenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-aminophenyl, 4-nitrophenyl, 4-methoxy3- A full-year rophenyl group is more preferred.

The cycloalkyl group having 3 to 6 carbon atoms in R ³ represents a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and a cyclohexyl group is preferable.

The monocyclic heterocyclic group represented by R ³ is the same or different and is a 5- to 8-cyclic aliphatic or aromatic containing 2 or 3 hetero atoms such as an oxygen atom, a nitrogen atom, and a sulfur atom. A mono-Hunch type heterocyclic group of an aromatic hydrocarbon; for example, a pyridyl group, a piperazinyl group, a piperidinyl group, a pyrimidinyl group, a pyrrolyl group, a vilanyl group, a furyl group, an oxazolyl group, a triazolyl group, a thixoxolyl group, A phenyl group, etc., which may be the same or different and include a 5- or 6-membered aliphatic or aromatic hydrocarbon containing one or two heteroatoms such as an oxygen atom, a nitrogen atom and a sulfur atom; A cyclic heterocyclic group is preferable, and a pyridyl group, a furyl group and a phenyl group are more preferable.

As the monocyclic heterocyclic group having a substituent of R ³ , a 5-promo-2-furyl group and a 5-chloro-2-phenyl group are preferable. R ³ is phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-phenyl, 2,3-difluorophenyl, 2,4-dichlorophenyl, 2,4-dichlorophenyl, , 6-Dichlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3,5-dibromophenyl, 5-bromo-2-chlorophenyl, 2,3,5-trichlorophenyl Group, 2,4,6-trichlorophenyl group, 2-chloro-4,5-difluorophenyl group, 4-methylphenyl group, 4-ethylphenyl group, 4-n-propylphenyl group, 4-isopropylphenyl group, 2,4,6-trimethylphenyl group, 4-trimethylphenyl group, 4-methoxyphenyl group, 4-methylthiophenyl group, 4-aminophenyl group, 4-nitrophenyl group, 4 Methoxy 3- Furuo port phenyl group, a cyclohexyl group, 5- bromo-2-furyl, 5-chloro-2 one thienyl group.

 General formula (1)

Wherein R ′, R ² and R ³ have the same meanings as described above,

Examples of the compound represented by are 2-ethyl-1- (4-one-year-old benzoyl) -1-5-methanesulfonylindole, and 1-1 (4-one-year-old benzoyl) -15-methane-sulfonyl 2-n- Propylindole,〗 -1 (4-promobenzoyl) —5 -Methanesulfonyl 2-π-propylindole, 1-1 (4-chlorobenzene) 1 -5-Methanesulfonyl 2-n-propylindole, 5-methanesulfonyl 1- (4-methylbenzoyl) 2- (π-propylindole), 5- (methanesulfonyl) -2-propyl-1-1 (4-trifluoromethylbenzoyl) indole, 1-1 (4-methylbenzoyl) N-zyl) 1-5-Methanesulfonyl 2-methylindole, 5-methanesulfonyl 11- (412-benzenyl) 1-2-π- Mouth pillindole, 1 1- (4-hydroxybenzoyl) 1 5-Methanesulfonyl 2- 1-n-propylindole, 1- (2,4-dichlorobenzene) 1-5-Methanesulfonyl 2-n-propylindole, 1 — (5-bromo-2-furoyl) 1 5-1 methanesulfonyl 2-n-propylindole, 5-methanesulfonyl 1-1 1 (4-methoxybenzoyl) 1 2—n-propylindole, 1—6 1- 5-Methanesulfonyl 2-n-propylindole,

1- (4-ethylbenzoyl) 1-5-Methanesulfonyl 2-n-propylindole, 1- (5-bromo-2-chlorobenzoyl) 1-5-Methanesulfonyl

2-n-propylindole, 5-methanesulfonyl 1-1- (4-methylthiobenzoyl) -1-2-n-propylindole, 1-1 (2,4,6-trichlorobenzoyl) -1-5-methanesulfonyl 2-n -Propylindole, 1 Benzoyl 5-5-Methanesulfonyl 2-n-Propylindole, 1- (4-isopropylbenzyl) 1 5-Methanesulfonyl 2-n-propylindole, 1-Cyclohexylcarbone 5-Methanesulfonyl 2-π-propylindole, 1-1 (5-chloro-2-tenol) 1 5-methanesulfonyl 2-n-propylindole, 1-1 (4-n-propylbenzyl) — 5-Methanesulfonyl-1-2-n-propylindole, 1- (3,5-dichlorobenzene) -1-5-methanesulfonyl 2-n-propylin 1,1- (2,3-difluorobenzyl) -1-5-methanesulfonyl 2-n-propylindole, 1- (3,4 dicyclobenzoyl) -1-5-methanesulfonyl-2-n-propylindole , 1- (2-Chloro-4,5-dibenzobenzoyl) -1-5-Methanesulfonyl 2-n-propylindole, 1-1 (3,5-dibromobenzoyl) -1 5-Methanesulfonyl 2-n —Propylindole, 1 1 (2,3,5-trik-opening benzoyl) —5—Methanesulfonyl 2-—n-Propylindole, 1

(2,4,6-trimethylbenzoyl) -1-5-methanesulfonyl 2-n-propylindole, 1-1 (2,6-dichlorobenzoyl) -1-5-methanesulfonyl 1-2-n-propylindole, 1-1- (4-methoxy-3-fluorobenzene) 1-5-methanesulfonyl 2-n-propylindole, 1-(4-bromobenzoyl) 1-5-methanesulfonylindole , 2-n-butylyl 1-1 (4-chlorobenzene) 1-5-methanesulfonylindole, 1-1 (4-cyclobenzene) 5-5-methanesulfonyl 2-n-pentylindole, 1 (4 Chlorobenzyl) 1 2— π—hexyl 5-methanesulfonylindole, 11

(4-cyclobenzoyl) 1-cyclopropylmethyl-5-methanesulfonyl indole, 2-aryl 1-11 (4-cyclobenzoyl) 1-5-methanesulfonyl indole, 1-1 (4chloro Benzoyl) 1-5-ethanesulfonyl-2-n-propylindole, 1- (4-benzobenzoyl) 1 5-n-propanesulfonyl-2-n-propylindole, 1- (4fluoro) Benzyl) 1-5—Methanesulfonyl 2 -— (Cyclohexene—11-yl) 1-indole, 1 1- (4-cyclohexylbenzoyl) 1-5-Methanesulfonyl 2- 2-phenylindole, 1-one

(4-chlorobenzene) 2-5-isoprobenylindole is preferred, and 1-1 (4-fluorobenzoyl) -15-methanesulfonyl 2-π-propylindole, 1 1- (4-promobenzoyl) -1-5-methanesulfonyl 2- 2-π-propylindole, 1- (4-chlorobenzoyl) -15-methanesulfonyl-2-n-provindindole are more preferred.

 The compounds of the present invention can also be obtained as hydrates.

 General formula (1)

In the formula, R ′, R ² and R ³ each have the same meaning as described above, and the compound represented by the general formula (2)

In the formula, RR ² and R ³ each have the same meaning as described above.

R ³ COOH (3)

Wherein R ³ has the same meaning as described above,

It is produced by reacting a reactive derivative of a carboxylic acid represented by The reactive derivative includes the acid anhydride and the acid chloride.

This reaction is carried out using a polar aprotic (aprotic) solvent in the presence of a base. The base at that time is an inorganic metal base, preferably sodium hydride, potassium hydride, more preferably hydrogen: sodium, or an organic base, preferably triethylamine, diisopropylethylamine, pyridine, 2, 6 —Dimethyl-41-aminoviridine is used. Further, as the aprotic polar solvent, dimethylformamide (DMF), dimethylacetamide, tetrahydrofuran (THF) and the like are used, and dimethylformamide is preferably used. The reaction temperature is preferably between 110 and 100 *, and particularly preferably between 0 and 30. This reaction is carried out by treating the compound of the general formula (2) with a base and then reacting the carboxylic acid chloride or the carboxylic acid anhydride of the general formula (3). The base to be used includes lithium diisoproviramide, lithium pistrimethylsilylamide, potassium pistrimethylsilylamide, sodium bistrimethylsilylamide, sodium hydride, potassium hydride, etc., preferably, sodium hydride is used. . The reaction solvent includes tetrahydrofuran, ether, dioxane, dimethyloxetane, dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like, and preferably dimethylformamide is used. The reaction is carried out at a temperature of 0 to 1001, preferably at a temperature of 0 to 30 ° C. The compounds represented by the general formula (2) are each produced by the following production method. Thus, the compound is reacted with a reactive derivative of the carboxylic acid of the above general formula (3) to produce a compound represented by the general formula (1).

The compound of the present invention can be produced, for example, as follows.

Wherein, R ⁷ represents a hydrogen atom or a linear or branched alkyl Le group having a carbon number〗 1-6, 8 ³ Oyobi 1¾ ^5, the same meanings as described above.

The reaction from compound 1 to compound 2 is performed in the presence of a base using an aprotic polar solvent. As the base at this time, an inorganic gold base, preferably sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, more preferably sodium hydride, or an organic base, preferably triethylamine, diisopropyl Ethylamine, pyridine, and 2,6-dimethyl-4-aminopyridine are used. As the abrotic polar solvent, dimethylformamide, dimethylacetamide, tetrahydrofuran and the like are used, and dimethylformamide is preferably used. The reaction temperature is preferably between 110 and 100, and particularly preferably between 0 and 30 ^. preferable.

 In the reaction from compound 2 to compound 3, compound 2 is dissolved in an ether solvent such as tetrahydrofuran, dimethoxyethane, and diethyl ether, and the solution is converted into an organic metal base, preferably lithium diisopropylamide (LDA) or lithium. It is added to a solution of xamethyldisilazane, n-butyllithium, more preferably lithium diisopropylamide in tetrahydrofuran or the like, and then trimethylsilyl chloride (TMSCI) is added dropwise.

 The reaction from compound 3 to compound 4 is carried out by reacting an alkyl carboxylic acid anhydride or an alkyl carboxylate, wherein the alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, with dichloromethane, tetra A Lewis acid is added to a solution of an organic solvent such as chloromethane or tetrachloroethane, and the mixture is stirred for a while and then a methane solution of compound 3 in dichloromethane is added dropwise. As the Lewis acid, an acid generally used for a Friedel-Crafts reaction is used, and preferably, aluminum chloride, polyphosphoric acid, boron trifluoride ether, sulfuric acid, antimony pentachloride, iron trichloride, and tin tetrachloride are used. Gallium trichloride is used, and more preferably, aluminum chloride is used. The reaction temperature is preferably 0 to 80 * C, more preferably 0 to 40 * C.

 The reaction from compound 4 to compound 5 can be performed by a solution of t-butylamine borane complex and aluminum chloride in dichloromethane or the like, or a mixture of sodium borohydride and dichloromethane by trifluoric acid. A solution of compound 4, such as dichloromethane, is added dropwise to the solution. The reaction temperature at this time is from 120 to 40, and preferably from 20 to 30.

The reaction from compound 5 to compound 6 is carried out by adding an organic gold base, preferably n-butyllithium or s-butyllithium, and more preferably n-butyllithium, to a solution of compound 5 in tetrahydrofuran or ether. Is added dropwise at 100 to 150 ^, preferably at 180 to 170, and after stirring for a while, dialkyl disulphide R ⁵ SSR ⁵ (R ⁵ is Represents the same meaning as), for example, Dimethydis This is done by dropping sulfide.

 The reaction from the compound 6 to the compound 7 is carried out by adding a compound 6 in a solution of an organic solvent such as dichloromethane, chloroform, tetrachloromethane, or the like, preferably in a solution of chloroform in metaclo-perbenzoic acid ( m CPBA). Alternatively, water may be added to a solution of the compound 6 in an alcohol, preferably a mixed solvent of methanol and tetrahydrofuran, with water of OXONE® (registered trademark).

 The reaction from the compound 7 to the compound 8 is carried out by adding an alcohol, preferably methanol, ethanol, or an abrotic polar solvent, preferably dimethylformamide or a mixed solvent of tetrahydrofuran and a polar solvent to water. Is dissolved or suspended, and an inorganic metal base such as sodium hydroxide, potassium hydroxide and lithium hydroxide is added to the reaction mixture. At this time, the reaction is carried out at 0 to 150 ° C, preferably at 80 to 100 ° C.

 The reaction from compound 8 to compound 9 is carried out in the presence of a base using an aprotic polar solvent. The base at that time is an inorganic gold base, preferably sodium hydride, potassium hydride, more preferably sodium hydride, or an organic base, preferably triethylamine, diisopropylethylamine, pyridine, 2,6-dimethyl-4. One aminoviridine is used. Further, as the abrotic polar solvent, dimethylformamide, dimethylacetamide, tetrahydrofuran and the like are used, and dimethylformamide is preferably used. The reaction temperature is preferably between 110 and 100, particularly preferably between 0 and 30.

In the general formula (1), R ′ is an alkylcarbonyl group in which the alkyl portion is a linear or branched alkyl group having 1 to 7 carbon atoms, or a linear alkyl group having 2 to 7 carbon atoms in the alkenyl portion. Or a compound having an alkenylcarbonyl group which is a branched alkenyl group or an alkynylcarbonyl group wherein the alkynyl moiety is a linear or branched alkynyl group having 2 to 7 carbon atoms. Operating with a metal, preferably sodium borohydride or lithium aluminum hydride First, it is converted to an alcohol form, and a protecting group is introduced into a hydroxyl group using t-butyldimethylsilyl chloride, methoxymethyl chloride, and the like. In the final step, hydrochloric acid, dilute sulfuric acid, sulfuric acid, tetrabutylammonium chloride are used. The compound can be produced by treating with a compound such as sodium fluoride or hydrogen fluoride-pyridine derivative to remove the protecting group and then oxidizing. As the oxidizing agent at this time, manganese dioxide, dimethyl sulfoxide, quinoxalyl chloride, pyridinium chloride and the like are used. Further, the compound of the present invention can be produced, for example, as follows.

In the formula, R ⁸ represents a linear or branched alkyl group having 1 to 7 carbon atoms, and A represents a halogen such as a fluorine atom, a chlorine atom, or a bromine atom! R ^a represents ^a hydrogen atom, a linear or branched alkyl group having 1 to 7 carbon atoms, and R ³ and R ⁵ have the same meanings as described above.

The reaction from Compound 10 to Compound I1 is carried out in the presence of a base using an aprotic polar solvent. As the base at this time, an inorganic metal base, preferably sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, more preferably water Sodium iodide or an organic base, preferably triethylamine, diisopropylethylamine, pyridine, 2,6-dimethyl-41-aminopyridine is used. As the aprotic polar solvent, dimethylformamide, dimethylacetamide, tetrahydrofuran and the like are used, and dimethylformamide is preferably used. The reaction temperature is preferably between 110 and 100, and particularly preferably between 0 and 30.

The reaction from compound 11 to compound 12 is carried out by dissolving compound 11 in an organic solvent such as tetrahydrofuran, dimethyloxyethane, and getyl ether, and dissolving the solution in an organic metal base, preferably lithium diisopropylamide, lithium hexamethyldisilazane. , N-butyllithium, more preferably lithium diisopropylamide, in a solution of tetrahydrofuran or the like, and then a straight-chain or branched alkyl halide having 1 to 7 carbon atoms: R ⁸ — A (wherein , R ⁸ and a are each as窻taste as above), preferably carried out dropwise straight銷or branched Arukiruhara I de carbon number〗 1-4.

The reaction from the compound 12 to the compound 13 or the reaction from the compound 11 to the compound 13 is carried out by adding a solution of the compound 12 or the compound 11 in tetrahydrofuran or ether or the like to an organometallic base, preferably π- Butyllithium, s-butyllithium, more preferably n-butyllithium, is preferably from 100 to -500C, preferably from 180 to 170. After dropping at C and stirring for a while, dialkyl disulfide: R ⁵ SSR ⁵ (R ⁵ has the same meaning as described above), for example, dimethyl disulfide is dropped. The reaction from compound 13 to compound 14 is performed by adding perfluorobenzoic acid to a solution of compound 13 in an organic solvent such as dichloromethane, chloroform and tetrachloromethane, and preferably to a solution of chloroform. Alternatively, the reaction may be carried out by adding suspended water of quinone to a solution of a mixed solvent of an alcohol of compound 13, preferably methanol, and tetrahydrofuran.

The reaction from compound 14 to compound 15 is carried out using an alcohol, preferably methanol, Compound〗 4 is dissolved or suspended in a solvent mixture of ethanol or an aprotic polar solvent, preferably a polar solvent of dimethylformamide or tetrahydrofuran, and water, and the reaction mixture is mixed with sodium hydroxide and water. This is performed by adding an inorganic gold-base such as potassium oxide or lithium hydroxide. The reaction temperature at this time is 0 to 150 ° C, preferably 80 to 100 ° C.

 The reaction from the compound 15 to the compound 16 is performed in the presence of a base using an aprotic polar solvent. The base at that time is an inorganic metal base, preferably sodium hydride, potassium hydride, more preferably sodium hydride, or an organic base, preferably triethylamine, diisopropylethylamine, pyridine, 2,6-dimethylene. 4-Aminoviridine is used. In addition, dimethylformamide, dimethylacetamide, tetrahydrofuran and the like are used as the aprotic polar solvent, and dimethylformamide is preferably used. The reaction temperature is preferably between 110 and 100 ° C., particularly preferably between 0 and 30 ^.

 Further, the compound of the present invention can also be produced, for example, as follows.

^ΒΓ

17 18 19 mCPBA CHCI ₃

In the formula, R ³ , R ⁵ and A have the same meaning as before, and R ^{1 Q} has 1 to 7 carbon atoms. A straight-chain or branched-chain alkyl group, a straight-chain or branched-chain alkenyl group having 2 to 7 carbon atoms, a chain- or branched-chain alkynyl group having 2 to 7 carbon atoms or one (CH ₂ ) _m — R ⁴ , wherein R ^lb is a hydrogen atom or a linear or branched alkyl group having 1 to 7 carbon atoms, a linear or branched alkenyl group having 2 to 7 carbon atoms, carbon number 2-7 straight or branched alkynyl group or a (CH _{2) m} - represents R ^4, m and R ⁴ are as defined above.

The reaction from the compound 17 to the compound 18 is carried out by dissolving the compound 17 in an ether-based solvent such as tetrahydrofuran, dimethyloxetane, and diethyl ether, and adding an inorganic base, preferably potassium hydride or hydrogen, to the solution. After adding sodium hydride, more preferably potassium hydride, and stirring for a while at 120 to 0, preferably at 10 to 0 ^, an organic gold base, preferably t-butyllithium, s-butyllithium , N-butyllithium, lithium diisopropylamide, more preferably t-butyllithium, preferably at 100-150 \ :, more preferably 180-170 ^, and then dialkyldisulfate. Id R ⁵ SSR ⁵ (wherein R ⁵ has the same meaning as described above), for example, by dropping dimethyl disulfide.

 The reaction from compound 18 to compound 19 is carried out in the presence of a base using an aprotic polar solvent. As the base at this time, an inorganic metal base, preferably sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, more preferably sodium hydride, or an organic base, preferably triethylamine, diisopropylamine Luethylamine, pyridine and 2,6-dimethyl-41-aminoviridine are used. As the aprotic polar solvent, dimethylformamide, dimethylacetamide, tetrahydrofuran and the like are used, and dimethylformamide is preferably used. The reaction temperature is preferably from 110 to 100, particularly preferably from 0 to 30 ° C.

The reaction from compound 19 to compound 20 is carried out by dissolving compound 19 in an organic solvent such as tetrahydrofuran, dimethyloxyethane, and getyl ether, and preparing the solution in the solution. Metal base, preferably n-butyllithium, s-butyllithium, t-butyllithium, lithium diisopropylamide, lithium hexamethyldisilazane, more preferably n-butyllithium, and then hexamethylphosphate Triamide (HMPA), N, N, N, N-tetramethylethylenediamine (TMEDA) or hexamethylphosphorustriamide (HMPT), preferably HMPA, and the alkyl moiety has 1 carbon atom. Alkyl halide which is a 廑 -chain or branched alkyl group having up to 7 carbon atoms, alkyl halide wherein the alkyl portion is a cycloalkyl group having 3 to 6 carbon atoms, cycloalkyl wherein the cycloalkyl portion is a cycloalkyl group having 3 to 6 carbon atoms Alkyl halide or alkenyl moiety that is an alkylmethyl group or a cycloalkylethyl group Halide is such straight town or branched alkenyl halide of 2-7 carbon atoms: R '° - A (wherein, R' ° and A are as defined above) conducted dropwise.

 The reaction from compound 20 to compound 21 or the reaction from compound 19 to compound 21 is a solution of compound 20 or compound 19 in an organic solvent of dichloromethane, chloroform and tetrachloromethane. Preferably, metachloroperbenzoic acid is added to the solution of black form. Alternatively, the reaction may be carried out by adding a suspension of xyxone to a solution of a compound 20 alcohol, preferably a mixed solvent of methanol and tetrahydrofuran. The reaction from compound 21 to compound 22 is carried out by reacting an alcohol, preferably methanol, ethanol, or an aprotic polar solvent, preferably a mixed solvent of a polar solvent such as dimethylformamide and tetrahydrofuran, with water, 21 is dissolved or suspended, and an inorganic metal base such as sodium hydroxide, potassium hydroxide or lithium hydroxide is added to the reaction mixture. At this time, the reaction is carried out at a temperature of 0 to 150 ° C., preferably 80 to 100 ° C.

The reaction from compound 22 to compound 23 is performed in the presence of a base using an aprotic polar solvent. The base at that time is an inorganic metal base, preferably sodium hydride, potassium hydride, more preferably sodium hydride, or an organic base, preferably Triethylamine, diisopropylethylamine, pyridine, and 2,6-dimethyl 4-aminobiidine are used. In addition, dimethylformamide, dimethylacetamide, tetrahydrofuran and the like are used as the aprotic polar solvent, and dimethylformamide is preferably used. The reaction temperature is preferably between 110 and 100 ^, particularly preferably between 0 and 30.

 In addition, the compound of the present invention can also be produced, for example, as follows.

In the formula, R ³ , R ⁵ and A have the same meaning as described above, R ¹¹ represents an aryl group or a heteroaryl group, R ¹² represents a methyl group, an ethyl group or an n-propyl group; ¹³ represents a hydrogen atom, a methyl group or an ethyl group, or R ¹² and R ¹³ together represent a (CH ₂ ) _π — group Here, n represents an integer of 2 to 4, and represents a branched alkenyl group having 3 to 7 carbon atoms, a cycloalkenyl group having 4 to 6 carbon atoms, an aryl group or a heteroaryl group.

Examples of the indole derivative compound produced by this production method include compounds 27, 28 and 29 in which R ¹² is a methyl group and R ¹³ is a hydrogen atom, and R ′ ² and R ^13, together with one (CH _{2) 4} - compound 27, 28 and 29, R is compound 26 and 30 is a phenyl group and intermediates that are, but each Isopurobe group, hexene one 1 Iru group cycloheteroalkyl is the phenyl group Compound 32 and the like.

The reaction from the compound 24 to the compound 25 is carried out by treating the compound 24 with a base and then reacting with tin chloride. Tin chloride, trimethyltin chloride, Toripuchi Ruchinkurorido, uses a Bok riff enyl Chin chloride, preferably, Toripuchi Ruchinkurorido _{(n- B u 3 S n CI} ) is used. The base used here includes lithium diisopropylamide, lithium bistrimethylsilylamide, potassium bistrimethylsilylamide, sodium pistrimethylsilylamide, sodium hydrogen hydride, potassium hydride, and the like. Use lithium diisopropylamide. Hexamethylphosphoric acid triamide, tetramethylethylenediamine and the like can be added to the reaction solution in order to improve the nucleophilicity of the generated carbanion. The reaction solvent includes tetrahydrofuran, ether, dioxane, dimethyloxetane, dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like, but preferably tetrahydrofuran is used. The reaction is carried out at a temperature of 110 to 100 ° C, preferably at a temperature of 78 to 0 ° C.

The reaction from compound 25 to compound 26, compound 25 Palladium Reagents and Ari Ruharaido or hetero aryl halides: R "- A (wherein, R ^'1 and A are as defined before SL) reacting The palladium reagent used is tetrakistriphenylphosphine palladium, bis (triphenylphosphine). Emissions) and the like palladium dichloride, but is preferably used bis (triphenylphosphine) palladium dichloride _{(P h 3 P) 2 P} d CI 2. The reaction solvent is preferably methanol or ethanol. The reaction is carried out at a temperature of from 0 to 100 ° C., preferably from 70 to 90 ° C.

 The reaction from the compound 24 to the compound 27 is carried out by subjecting the compound 24 to a base treatment, followed by the following general formula: c = o

R ¹³ CH2

Wherein, R ^{1 2} and R ^{1 3} represents the same窻昧said,

The reaction is carried out by reacting the ketone represented by Examples of this ketone include acetone and cyclohexanone. The base used herein includes lithium diisopropylamide, lithium bistrimethylsilylamide, potassium bistrimethylsilylamide, sodium pistrimethylsilylamide, sodium hydride, potassium hydrate, and the like. I have. Examples of the reaction solvent include tetrahydrofuran, ether, dioxane, dimethyloxetane, dimethylformamide, dimethylacetamide, dimethylsulfoxide, and the like. Preferably, tetrahydrofuran is used. The reaction is carried out at a reaction intensity of 0 to 100, preferably 0 to 30 *.

 The reaction from the compound 27 to the compound 28 is carried out by treating the compound 27 with an acid. The acid to be used includes a catalytic amount or a small amount of toluenesulfonic acid, sulfuric acid, trifluorosulfonic acid, trifluoromethanesulfonic acid, boron fluoride ether loach, and the like, preferably toluene sulfonic acid. As the reaction solvent, benzene, toluene, and xylene are used, and toluene is preferably used. The reaction is carried out at a temperature of from 0 to 200, preferably at a temperature higher than the boiling point of the solvent used.

The reaction from compound 28 to compound 29 or the reaction from compound 26 to compound 30 is carried out by oxidizing compound 28 or compound 26, respectively. Use As the oxidizing agent, there may be mentioned peroxybenzoic acid and sodium periodate. Preferably, peroxybenzoic acid is used. The reaction is carried out at a temperature of 110 to 30 ° C, preferably at 0 ° C. As a reaction solvent, chloroform, dichloromethane, tetrachloromethane, tetrahydrofuran, water and the like are used, and preferably, chloroform is used. Alternatively, it may be carried out by adding the suspension water of Xixon to a solution of an alcohol of compound 28 or compound 26, preferably a mixed solvent of methanol and tetrahydrofuran.

 The reaction from compound 29 or compound 30 to compound 31 is performed by hydrolyzing compound 29 or compound 30 with a base, respectively. The base to be used includes sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide, magnesium hydroxide and the like, but preferably potassium hydroxide is used. The reaction is carried out at a temperature of from 0 to 100 ° C., preferably from 80 to 100 ° C. As the reaction solvent, water, methanol, ethanol, propanol, tetrahydrofuran or a mixed solvent thereof is used, and preferably, methanol is used.

 The reaction from the compound 31 to the compound 32 is carried out by treating the compound 31 with a base, followed by the general formula (3):

R ³ COOH (3)

Wherein R ³ has the same meaning as described above.

The reaction is carried out by reacting a reactive derivative of a carboxylic acid represented by, for example, carboxylic acid chloride or carboxylic anhydride. The base to be used includes lithium diisopropidoviramide, lithium bistrimethylsilylamide, potassium bistrimethylsilylamide, sodium pistrimethylsilylamide, sodium hydride, potassium hydride, and the like, and preferably, sodium hydride is used. . The reaction solvent includes tetrahydrofuran, ether, dioxane, dimethyloxetane, dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like, and preferably dimethylformamide is used. The reaction is carried out at a temperature of 0 to 100 ^, preferably at 0 to 3 ^ C. In addition, the compounds of the present invention other than the above-mentioned compounds can be produced by the same method as in the above-mentioned production method or by a production method in which a part is appropriately changed depending on the target compound to be produced.

 The compounds of the present invention can also be produced by applying the specific production methods described in the examples.

 INDUSTRIAL APPLICABILITY The compound of the present invention has an inhibitory activity on xygenase-12, and is useful as an anti-inflammatory agent. The compound of the present invention can be administered orally or parenterally, such as oral, intravenous injection, mucosal application, and transdermal application. The dosage in that case is 3 to 15 Omg Zkg for oral and 1 to 5 OmgZkg for parenteral per day. When these compounds are administered as pharmaceuticals, they can be formulated using conventional formulation techniques, such as tablets, capsules, powders, granules, suppositories, creams, soft S agents, and aqueous solutions It can be used as a solid or liquid form such as an emulsion, an oily agent or a suspension.

 Further, in this case, it is possible to use excipients, disintegrants, lubricants, binders, preservatives, stabilizers, osmotic pressure adjusting agents or bases which are commonly used in the formulation. it can.

 Examples of these additional ingredients include glucose, lac! Examples include starch, starch, carboxymethylcellulose, magnesium stearate, talc, liquid paraffin, polyvinyl alcohol, vegetable oil, polyalkylene glycol, and the like.

 It can also contain other pharmaceutical ingredients.

Example

 Hereinafter, the production of the compound of the present invention will be described in more detail with reference to Examples, but the present invention is not limited by these Examples.

 In order to show the usefulness of the compound of the present invention, pharmacological test results on COX-2 inhibitory effects of representative compounds of the compound of the present invention are shown in Test Examples.

Tables 1 to 3 show the chemical structural formulas of the example compounds. c = o

 J

 R Example

R ¹ R ²

Number

One Et eS0 _2-

1 6 — n-Pr eSO,-■ SMe Table 2

Illustration

R ¹ R 2

 CI

 2 5 — n-Pr MeSO, — -CI

Three

Example

R ¹

3 2 One H eS0 ₂ —--Br 3 3 -nC ₄ H ₉ MeS0 ₂ —— -CI 3 4 -n-CgH!, MeS0 ₂ — -CI

3 5 1 nC ₆ H ₁₃ eS0 ₂ — -CI 3 6 MeS0 ₂ — -CI 3 7 1 CC: CH ₂ MeSO, —

H ₂ H ■ CI 8 —n-Pr EtS0 ₂ — • CI 9 —n-Pr n-PrSO Factory -CI

Reference example 1

 1- (benzenesulfonyl) -1-2-ethyl -5-methylthioindole

 To a solution of 1- (benzenesulfonyl) -1-5-proethyl-2-ethylindole (810 mg) in tetrahydrofuran (20 ml) under a nitrogen stream at 1 78 ^ n-butyllithium (1.65 M , N-hexane solution, 1.75 ml) was added dropwise. After stirring the reaction mixture at the same temperature for 15 minutes, dimethyl disulphide (272 mg) was added, and the mixture was further stirred at 178 for 2 hours. Then, the reaction mixture was returned to room temperature and reduced under reduced pressure. The obtained residue was poured into a 1N aqueous solution of sodium hydroxide, and extracted with ethyl nitrate. The ethyl persulfate layer was washed successively with water and saturated saline, dried over anhydrous magnesium sulfate, filtered, and boxed. The obtained residue was subjected to silica gel column chromatography, and the desired product (256 mg) was obtained using ethyl persulfate: π-hexane (1: 8) as an elution solvent.

NMR (C DC I ₃ ) <5 values: 1.30 (3 H, t, J = 7.4 Hz), 2.47 (3 H, s), 2.99 (2 H, q, J = 7.4 Hz), 6.32 (1 H, s), 7.19 (1 H, dd, J = 2.0 Hz, 8.8 Hz), 7.28-7.56 ( 4 H, m), 7.71 (2 H, d, J = 6.8 Hz), 8.09 (1 H, d, J = 8.6 Hz)

Reference example 2

11- (benzenesulfonyl) -1-2-ethyl-5-methanesulfonylindole In a chloroform solution (3 ml) of the compound of Reference Example 1 (66 Omg), at 0 at 70% metaclo-perbenzoic acid (89. 5 mg) and stirred at the same temperature for 1 hour. Next, the reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate and extracted with chloroform. The chloroform layer was washed with saturated saline, dried over anhydrous magnesium sulfate, passed through, and compressed. Here, the obtained residue was subjected to silica gel column chromatography, and the desired product was separated using chloroform: methanol (50: 1) as an elution solvent, and further recrystallized from acetone Zn-hexane. The desired product crystals (40.8 mg) were obtained. NMR (CDC I ₃ ) value: 1.36 (3 H, t, J = 7.4 Hz), 3.00—3.18 (2 H, m), 3.08 (3 H, s) , 6.51 (1H, s), 7.40—7.90 (6H, m), 8.06 (1H, d, J = 1.1 Hz), 8.37 (1 H, d, J = 8.9 H 2)

Reference example 3

 2-ethyl-5-methanesulfonylindole

 To a methanol solution (5 ml) of the compound of Reference Example 2 (48. Omg) was added an aqueous solution of IN—potassium hydroxide (650 I), and the mixture was heated under reflux for 2 hours. Next, the reaction mixture was concentrated, and the obtained residue was suspended in black-mouthed form, washed with water and saturated saline solution H, dried over anhydrous magnesium sulfate, concentrated and concentrated. The obtained residue was subjected to preparative thin-layer silica gel chromatography, and the desired product (27.7 mg) was obtained using chloroform (20: 1) as a developing solvent.

NMR (C DC I ₃ ) <5 values: 1.36 (3 H, t, J = 7.6 H 2), 2.82 (2 Η, q, J = 7.6 ζ), 3.07 (3Η, s), 6.36 (1Η, s), 7.40 (1Η, d, J = 8.6H2), 7.78 (1H, dd, J = 1.9H) z, 8.6 H z), 8.14 (1 H, s), 8.62 (1 H, bs)

2-Ethyru (4-fluorobenzoyl) -1-5-Methanesulfonylindole A solution of the compound of Reference Example 3 (20.Omg) in dimethylformamide (2 ml) at 0% with 60% hydrogenation (5%) .4 mg) was added. After the reaction mixture was stirred at the same temperature for 15 minutes, 4-fluorofurobenzoyl chloride (21. mg) was added, and the mixture was further stirred at room temperature for 2 hours. Therefore, the reaction mixture was poured into a saturated aqueous solution of ammonium chloride and extracted with toluene. The toluene was washed with a saturated saline solution, dried over anhydrous magnesium sulfate, destroyed and concentrated. Here, the obtained residual brew is subjected to thin-layer silica gel column chromatography, and the target substance is separated using chloroform: methanol (100: 1) as an elution solvent, and acetone-hexane is further added. The crystals were recrystallized from sun to give the desired crystals (18.1 mg).

NMR (CDC I ₃ ) <5 values: 1.29 (3 H, t, J = 7.3 Hz), 2.85

(2 H, q, J = 7.3 Hz), 3.06 (3 H, s), 6.62 (1 H, s), 7.07 (1 H, d, J = 8.9 H z), 7.3 (2 H, m), 7.8

(2 H, m), 8.14 (1 H, s)

Reference example 4

 1- (benzenesulfonyl) -1-5-bromo-2-propionylindole A suspension of propionic anhydride (957 mg) and aluminum chloride (1.96 g) in methylene chloride (6 ml) was stirred at room temperature for 15 minutes. . Then, a solution of 11- (benzenesulfonyl) -15-promo-2-trimethylsilylindole (1.0 g) in methylene chloride (6 ml) was added, and the mixture was further stirred at the same temperature for 1 hour. Next, the reaction mixture was poured into ice water, made basic with sodium hydroxide, and extracted with methylene chloride. The methylene chloride layer was washed successively with water and saturated saline, dried over anhydrous magnesium sulfate, concentrated and concentrated. The obtained residue was subjected to silica gel column chromatography, and the desired product (78 Omg) was obtained using n-hexane (1: 4) as an elution solvent.

NMR (CDC I ₃ ) <5 values: 1.25 (3 H, t, J = 7.3 Hz), 2.98 (2 H, q, J = 7.3 Hz), 6.93 ( 1 H, s), 7.31 -7.66 (4 H, m), 7.68 (1 H, d, J = 1.9 Hz), 7.86-8.08 (3 H, m )

Reference example 5

 1- (benzenesulfonyl) -5-bromo-2-n-propylindole

To a methylene chloride suspension (1 30 ml) of butylamine (2.22 g) and aluminum chloride (3.40 g) in methylene chloride solution (10.0 g) 30 ml) was added. After stirring the reaction mixture for 1 hour, ice was added to the reaction solution, and the water shoe was made basic with sodium hydroxide. Next, separate the organic layer After washing with water and saturated saline, the extract was dried over anhydrous magnesium sulfate, passed through, and concentrated. The obtained residual brew was subjected to silica gel column chromatography, and the desired product (6.67 g) was obtained using methylene chloride: π-hexane (2: 3) as an elution solvent.

NMR (C DC I ₃ ) <5 values: 1.02 (3 H, t, J = 7.3 Hz), 1.77-1.91 (2 H, m), 2.94 (2 H , T, J = 7.3 Hz), 6.33 (1 H, s), 7.29-7.43 (4 H, m), 7.5 (2 H, m), 7.70 ( 1 H, d, J = 7.8 Hz), 8.04 (1 H, d, J = 8.9 Hz) Reference example 6

 1- (benzenesulfonyl) -1-5-methylthio-1-n-propylindole The compound of Reference Example 5 (1.30 g), dimethyl disulphide (295 mg) and n-butyllithium (1.65 n-hexane) Using the solution (3.13 ml), the desired product (597 mg) was obtained in the same manner as in Reference Example 1.

NMR (CDC I ₃ ) <5 values: 1.01 (3 H, t, J = 7.3 Hz), 1.65-1.87 (2 H, m), 2.49 (3 H, s ), 2.94 (2 H, t, J = 7.3 Hz), 6.32 (1 H, s), 7.20 (1 H, dd, J = 1.6 Hz, 8.9 Hz), 7.31 (1H, s), 7.35—7.57 (3H, m), 7.71 (2H, d, J = 7.6Hz), 8. 08 (1 H, d, J = 8.9 Hz) Reference Example 7

 1- (benzenesulfonyl) -1-5-methanesulfonyl 2-n-propylindole

 The target product (392 mg) was obtained in the same manner as in Reference Example 2 by using the compound of Reference Example 6 (528 mg) and 70% metaclotobenzoic acid (754 mg).

NM R (C DC I ₃ ) <5 values: 1.04 (3 H, t, J = 7.3 Hz), 1.7 1 — 1.87 (2 H, m), 2.99 (2 H, t, J = 7.3 Hz, 3.01 (3 H, s), 6.51 (1 H, s), 7.20—7.33 (3 H, m), 7.75 (2H, d, J = 7.8Hz), 7.81 (1H, dd, J = 1.6, 8.8Hz), 8.05 (1H, d, J = 1. 6 Hz), 8.35 (1 H, d, J = 8.8 Hz)

Reference Example 8

 5-Methanesulfonyl 2-n-propylindole

 Using the compound of Reference Example 7 (27. Omg) and a 1 N aqueous solution of potassium hydroxide (378I), the target product (16. Omg) was obtained in the same manner as in Reference Example 3.

NMR (C DC I ₃ ) <5 values: 0.96 (3 H, t, J = 7.4 Hz), 1.60- 1.80 (2 H, m), 2.69 (2 H, t, J = 7.3 Hz), 3.00 (3 H, s), 6.30 (1 H, s), 7.33 (1 H, d, J = 8.4 Hz),

7.56 (1 H, d d, J = 1.8 H z, 8.4 H z), 8.07 (1 H, s), 8.4 1 (1 H, b s)

Example 2

 1-(4 years old robenzoyl) 1-5-methanesulfonyl 2-n-propyl indole

 A method similar to that of Example 1 using the compound of Reference Example 8 (1 4. Omg), 4 1-year-old benzoyl chloride (1 4. Omg) and 60% sodium hydride (3.5 mg). Thus, the desired product (19.2 mg) was obtained.

NMR (C DC I ₃ ) δ value: 0.95 (3 Η, t, J = 7.3 Hz), 1.57-1.76 (2 H, m), 2.82 (2 H, t , J = 7.6 Hz), 3.06 (3 H, s), 6.61 (1 H, s), 7.05 (1 H, d, J = 8.6 Hz), 7 . 1 4-7. 32 (2 H, m), 7.58 (1 H, dd, J = 1.6 Hz,

8.6 Hz), 8.14 (1 H, d, J = 1.6 Hz)

Example 3

1- (4-promobenzoyl) 1-5-Methanesulfonyl 2-n-propylindole Using the compound of Reference Example 8 (90.Omg), 4-monobromobenzoyl chloride (125 mg) and 60% sodium hydride (22.8 mg), the target compound (11 Omg) was obtained in the same manner as in Example 1. ).

NR (C DC I ₃ ) <5 value: 0.95 (3 H, t, J = 7.4 Hz), 1.55-1.75 (2 H, m), 2.81 (2 H, t, J = 7.6 Hz, 305 (3 H, s), 6.60 (1 H, s), 7.55 (1 H, d, J = 8.9 Hz), 7 48- 7.78 (5 H, m), 8.13 (1 H, s)

Example 4

 1- (4-methylbenzoyl) 1-Methanesulfonyl 2-n-propylindole

 Using the compound of Reference Example 8 (90.Omg), 4-monobenzobenzoyl chloride (99.6 mg) and 60% sodium hydride (22.8 mg), the target compound was obtained in the same manner as in Example 1. 1 15 mg).

NM R (CDC I ₃ ) (5 values: 0.95 (3 H, t, J = 7.4 Hz), 1.55—1.78 (2 H, m), 2.81 (2 H, t, J = 7.6 Hz), 3.06 (3 H, s), 6.60 (1 H, s), 7.05 (1H, d, J = 8.6 Hz), 7 5 1 (2 H, d, J = 8.6 Hz), 7.58 (1 H, dd, J = 1.8 Hz, 1.7 Hz), 7.68 (2 H, d , J = 8.6 Hz), 8.13 (1 H, d, J = 1.7 Hz)

Example 5

 5-Methanesulfonyl 1-1 (4-methylbenzoyl) 1-2-π-propylindole

 Using the compound of Reference Example 8 (90. Omg), 4-monomethylbenzoyl chloride (88. Omg) and 60% sodium hydrofluoride (22.8 mg), the desired compound (126 mg) was obtained in the same manner as in Example 1. ).

NR (CDC I ₃ ) (5 values: 0.91 (3 H, t, J = 7.4 Hz), 1.56- 1.78 (2 H, m), 2.48 (2 H, t, J = 7.6 Hz), 2.83 (3 H, s), 3.05 (3 H, s), 6. 59 (1 H, s), 7.04 (1 H, d, J = 8.8 Hz), 7.32 (2 H, d, J = 8.4 Hz), 7.55 (1 H , dd, J = 1.7 Hz, 8.8 Hz), 7.62 (1 H, d, J = 8.4 Hz), 8.12 (1 H, d, J = 1. 7 Hz)

Example 6

 5-Methanesulfonyl 2-n-propyl-1- (4-trimethyl romethylbenzoyl) Indole

 A method similar to that of Example 1 using the compound of Reference Example 8 (90. Omg), 4-triflurylmethyl benzoyl chloride (119 mg) and 60% sodium hydride (22.8 mg). Thus, the desired product (145 mg) was obtained.

NM R (C DC I ₃ ) <5 values: 0.95 (3 H, t, J = 7.4), 1.56—1.80 (2 H, m), 2.79 (2 H, t , J = 7.6 Hz), 3.06 (3 H, s), 6.63 (1 H, s), 7.03 (1 H, d, J = 8.6 Hz), 7. 5 9 (1 H, dd, J = 1.7 Hz, 8.6 Hz), 7.73-7.96 (4 H, m), 8.14 (1 H, d, J = 1 .7 Hz)

Reference Example 9

 5-Methanesulfonyl 2-methylindole

 1- (benzenesulfonyl) -1-5-methanesulfonyl 2-methylindole (250 mg) and 1N aqueous hydroxide solution (1.43 ml) in the same manner as in Reference Example 3 38 mg).

NMR (CDC I ₃ ) «5 values: 2.50 (3 H, s), 3.07 (3 H, s), 6.37 (1 H, s), 7.40 (1 H, d, J = 8.4 Hz), 7.67 (1 H, dd, J = 1.6 Hz, 8.4 Hz), 8.14 (1 H, s), 8.19 (1 H, bs)

Example 7 ^-(4-chlorobenzene) 1-5-Methanesulfonyl 2-methylindole The compound of Reference Example 9 (72. Omg), 4-cyclobenzoyl chloride (90.3 mg) and hydrogenated sodium Then, the desired product (116 mg) was obtained in the same manner as in Example 1 using the compound (20.6 mg).

NR (CDC I ₃ ) <5 values: 2.44 (3 H, s), 3.07 (3 H, s), 6.57 (1 H, s), 7.18 (1 H, d, J = 8.6 Hz), 7.5 1 (2 H, d, J = 8.4 Hz), 7.61 (1 H, dd, J = 1.6 Hz, 8.6 Hz ), 7.68 (2 H, d, J = 8.4 Hz), 8.12 (1 H, d, J = 1.6 Hz)

Example 8

 5-Methanesulfonyl 1-11 (412-benzoyl) 1 2-π-propylindole

 The same procedure as in Example 1 was carried out using the compound of Reference Example 8 (200.Omg), 412 benzoyl chloride (312 mg) and 60% sodium hydride (50.Omg), and the target compound was obtained. (206 mg) was obtained.

NMR (CDCI ₃ ) <5 values: 0.95 (3 H, t, J = 7.3 Hz), 1.64 1.73 (2 H, m), 2.78 (2 H, t, J = 7.6 Hz), 3.06 (3 H, s), 6.65 (1 H, s), 7.05 (1 H, d, J = 8.6 Hz), 7.60 (1 H, dd, J = 1.6 Hz, 8.6 Hz), 7.90 (2 H, d, J = 8.6 Hz), 8.15 (1 H, d, J = 1.6 Hz), 8.39 (2 H, d, J = 8.6 Hz)

Example 9

 1- (4-hydroxybenzoyl) -1-5-methanesulfonyl 2-n-propylindole

The compound of Reference Example 8 (100.Omg), 4-benzoic acid, Using the obtained 4-iodobenzoyl chloride (223 mg) and 60% sodium hydride (25.Omg), the same operation as in Example 1 was performed to obtain the desired product (172 mg).

NM R (CDC I ₃ ) (5 values: 0.95 (3 H, t, J = 7.3 Hz), 1.6 1-1-73 (2 Η, m), 2.81 (2 H , t, J = 7.6 Hz), 3.06 (3

H, s), 6.60 (ΊH, s), 7.05 (1H, d, J = 8.9Hz),

7.44 (2 H, d, J = 8.3 Hz), 7.58 (1 H, dd, J = 1.7 Hz, 8.9 Hz), 7.90 (2 H, d , J = 8.3 Hz), 8.13 (1 H, d, J = 1.7 Hz)

Example 10

 1-1- (2,4-dichlorobenzene) 1-5-Methanesulfonyl 2-π-Propyrindole

 The same operation as in Example 1 was performed using the compound of Reference Example 8 (100.Omg), 2,4-diclo-benzobenzoyl chloride (176 mg) and 60% sodium hydride (25.Omg). (133 mg).

NM R (CDC I ₃ ) δ value: 0.95 (3 Η, t, J = 7.3 Hz), 1.68-

I. 79 (2 H, m), 2.64-2.73 (2 H, m), 3.06 (3 H, s), 6.56 (1 H, s), 7.14-7 32 (2 H, m), 7.58 (1 H, dd, J = 1.6 Hz, 8.6 Hz), 8.14 (1 H, d, J = 1.6 Hz) )

Example 1 1

 1- (5-bromo-2-furoyl) 1-5-methanesulfonyl 2-n-propylindole

The compound of Reference Example 8 (80 · Omg), 5-promo-2-furocarboxylic acid and 5-chlorobromochloride (360 mg) obtained from sodium chloride and 60% sodium hydride (20.Omg) ) To perform the same operation as in Example 1, (1.12 mg) was obtained.

NMR (C DC I ₃ ) <5 values: 0.97 (3 H, t, J = 7.3 Hz), 1.66-1.79 (2 H, m), 2.82 (2 H, t, J = 7.6 Hz, 3.08 (3 H, s), 6.60 (1 H, s), 6.64 (1 H, d, J = 3.3 Hz), 7 23 (1 H, d, J = 3.3 Hz), 7.3 1 (1 H, d, J = 8.9 Hz), 7.67 (1 H, dd, J = 1.6 H z, 8.9 H z), 8.13 (1

H, s)

Example 1 2

 5-Methanesulfonyl 1-1 (4-methoxybenzoyl) 1 2-π-propyl indole

 The same operation as in Example 1 was carried out by using the compound of Reference Example 8 (100. Omg), 4-methoxybenzoyl chloride (13 mg) and 60% sodium hydride (25. Omg). (70. Omg).

NMR (CDC I ₃ ) <5 values: 0.97 (3 H, t, J = 7.3 Hz), 1.66—

I. 78 (2 H, m), 2.87 (2 H, t, J = 7.3 Hz), 3.09 (3 H, s), 3.94 (3 H, s), 6. 6 1 (1H, s), 7.02 (2H, d, J = 8.9Hz), 7.10 (1H, d, J = 8.6Hz), 7.58 ( 1 H, d, J = 8.6 Hz), 7.74 (2 H, d, J = 8.9 Hz), 8. 16

(1 H, s)

Example 13

 1 1 (6-nicotinoyl) 1 5-methanesulfonyl 2-n-propyl indole

The compound of Reference Example 8 (100.Omg), 6-chloronicotinoyl chloride (446mg) obtained from 6-chloronicotinic acid and thionyl chloride and 60% sodium hydride (50.Omg) were added. The same procedures as in Example 1 were carried out to obtain the desired product (108 mg). NR (C DC I ₃ ) <5 value: 0.96 (3 H, t, J = 7.3 Hz), 1.64 1.77 (2 H, m), 2.79 (2 H, t, J = 7.3 Hz), 3.07 (3 H, s), 6.64 (1 H, s), 7.12 (2 H, d, J = 8.6 Hz), 7.53 (1 H, d, J = 8.3 Hz), 7.63 (1 H, dd, J = 1.7 Hz, 8.6 Hz), 8.01 (1 H, dd , J = 2.6 Hz, 8.3 H 2), 8.15 (1 H, d, J = 1.7 Hz), 8.69 (1 H, d, J = 2.6 H z)

Example 14

 1- (4-Ethylbenzoyl) -1-5-Methanesulfonyl 2-n-propylindole

 Using the compound of Reference Example 8 (100. Omg), 4-ethylbenzoyl chloride (142 mg) and 60% sodium hydride (25. Omg), the same operation as in Example 1 was carried out to obtain the desired compound (1 32 mg).

NMR (CDC I ₃ ) δ value: 0.94 (3 Η, t, J = 7.3 Hz), 1.31 (3 H, t, J = 7.6 Hz), 1.60- 1.75 (2 H, m), 2.73—2.89 (4 H, m), 3.06 (3 H, s), 6.59 (1 H, s), 7.04 (1 H, d, J = 8.6 Hz, 7.34 (2 H, d, J = 8.3 Hz), 7.55 (1 H, dd, J = 1.7 Hz, 8. 6 H z), 7.64 (2 H, d, J = 8.3 H z), 8.12 (1 H, d, J = 1.7 H z)

Example 15

 ^-(5-Promo 2-Benzoyl) 1-5-Methanesulfonyl 2- n-propylindole

 The same procedure as in Example 1 was carried out using the compound of Reference Example 8 (100.Omg), 5-promo-2-benzobenzoyl chloride (533mg) and 60% sodium hydride (25.Omg) to obtain the target compound. (18 Omg).

NR (with CDC) <5 value: 0.96 (3H, t, J = 7.3Hz), 1.66— 1.78 (2 H, m), 2.72 (2 H, m), 3.06 (3 H, s), 6.59 (1 H, s), 7.21 (1 H, d, J = 8.6 Hz), 7.37 (1 H, d, J = 9.2 Hz), 7.62-7.69 (3 H, m), 8. 09 (1 H, s)

Example 16

 5-Methanesulfonyl 11- (4-methylthiobenzoyl) 1 2-n-Propylindole

 Performed using the compound of Reference Example 8 (80.Omg), 4-methylthiobenzoyl chloride (127 mg) obtained from 4-methylthiobenzoic acid and thionyl chloride and 60% sodium hydride (20.Omg). The same operation as in Example 1 was performed to obtain the desired product (129 mg).

NM R (C DC I ₃ ) δ value: 0 · 95 (3Η, t, J = 7.3 Hz), 1.59-1.75 (2H, m), 2.56 (3H, s), 2.84 (2H, t, J = 7.6Hz), 3.06 (3H, s), 6.59 (1H, s), 7.07 (1H, d, J = 8.6Hz), 7.31 (2H, d, J = 8.3Hz), 7.56 (1H, dd, J = 1.7H z, 8.6 Hz), 7.64 (2 H, d, J = 8.3 Hz), 8.13 (1 H, s)

Example 17

 1-(2,4,6-trichlorobenzene) 1-5-Methanesulfonyl 2-π π-propylindole

 The same operation as in Example 1 was carried out using the compound of Reference Example 8 (100. Omg), 2,4,6-triclomethylbenzoyl chloride (205 mg) and 60% sodium hydride (25.Omg). The desired product (101 mg) was obtained.

NMR (C DC I ₃ ) <5 values: 1.01 (3 H, brs), 1.77 (2 H, brs), 3.07 (5 H, brs), 6.5 3- 8.1 8 (6 H, m)

Example 18 1 Benzoyl 5-methanesulfonyl 2-propylindole

 The compound of Reference Example 8 (80. Omg), benzoyl chloride (95.6 mg) and

The same operation as in Example 1 was performed using 60% sodium hydride (20. Omg) to obtain the desired product (52 mg).

NMR (CDC I ₃ ) <5 values: 0.95 (3 H, t, J = 7.3 Hz), 1.64 1.77 (2 H, m), 2.82 (2 H, t, J = 7.3 Hz), 3.06 (3 H, s), 6.60 (1 H, s), 7.03 (1 H, d, J = 8.9 Hz), 7 46-7.73 (5 H, m), 8.09-8. 17 (2 H, m)

 Example 19

 1- (1-^-S-propylbenzyl) -1-5-Methanesulfonyl 2-π-Propylindole

 Compound of Reference Example 8 (80.Omg), 4-isopropylbenzoic acid and 4-isopropylbenzoyl chloride obtained from sodium chloride (124 mg) and 60% sodium hydride (20.Omg) And the same procedure as in Example 1 was performed to obtain the desired product (86 mg).

NMR (CDC I ₃ ) <5 values: 0.94 (3 H, t, J = 7.3 Hz), 1.31 (6 H, d, J = 7.1 Hz), 1. 62-1.79 (2 H, m), 2.83 (2 H, t, J = 7.6 Hz), 2.94-3.16 (4 H, m), 6.59 (1 H, s), 7.04 (1H, d, J = 8.8Hz), 7.37 (2H, d,

J = 8.3 Hz, 7.52-7.58 (1 H, m), 7.66 (2 H, d, J

= 8.3 Hz), 8.1 2-8.1 6 (1 H, m)

Example 20

 1-cyclohexylcarbonyl 5-5-methanesulfonyl 2-n-propylindole

Example 1 was repeated using the compound of Reference Example 8 (〗 20.Omg), cyclohexylcarbonyl chloride (148 mg) and 60% sodium hydride (30.Omg). The same operation was performed to obtain the desired product (109 mg).

NM R (C DC I ₃ ) δ value '丄 04 (3 Η, t, J = 7.3 Hz), 1.19-2.08 (1 3 H, m), 2.94 (2 H , T, J = 7.6 Hz, 3.08 (3 H, s), 6.52 (1 H, s), 7.77-7.84 (2 H, m), 8.10 (1 H, s)

Example 2 1

 1- (5-chloro-2-tenol) 1-5-methanesulfonyl 2-n-propylindole

 The compound of Reference Example 8 (100.Omg), 5-chloro-2-thiophenecarboxylic acid and thionyl chloride obtained 5-chlorothenoyl chloride (152 mg) and 60% sodium hydride (25.Omg) ) To obtain the desired product (101 mg).

NMR (CDC I ₃ ) <5 values: 0.97 (3 H, t, J = 7.3 Hz), 1.65-1.78 (2 H, m), 2.86 (2 H, t , J = 7.6 Hz), 3.08 (3 H, s), 6.59 (1 H, s), 7.00 (1 H, d, J = 4.0 Hz), 7. 32 (1 H, d, J = 4.OHz), 7.37 (1 H, d, J = 8.6 Hz), 7.64 (1 H, dd, J = 1.7 Hz, 8.6 Hz), 8.14 (1 H, d, J = 1.7 Hz)

Example 22

 1-(4-n-propyl benzoyl) 1-5-methanesulfonyl 2-n-pro-bilindole

 Compound of Reference Example 8 (100.Omg). 4-N-propylbenzoyl chloride (153 mg) obtained from 4-n-propylbenzoic acid and thionyl chloride and 60% sodium hydride (25.Omg) ) And the same operation as in Example 1 was carried out to obtain the desired product (97 mg).

NMR (CDC I ₃ ) δ value: 0.9 1-1.07 (6 Η, m), 1.60—1.7 9 (4 H, m), 2.71 (2 H, t, J = 7.4 Hz), 2.82 (2 H, d, J = 7.4 Hz), 3.06 (3 H, s), 6.59 (1 H, s), 7.04 (1 H, d, J = 8.9 Hz), 7.32 (2 H, d, J = 8.3 Hz) , 7.54 (1H, d, J = 8.9Hz), 7.64 (2H, d, J = 8.3Hz), 8.12 (1H, s)

Example 23

 1 One (3,5-dichlorobenzene) — 5-Methanesulfonyl 2-n-Propyindole

 The same operation as in Example 1 was carried out using the compound of Reference Example 8 (100.Omg), 3,5-dicyclopentabenzoyl chloride (176 mg) and 60% sodium hydrogen hydride (25.Omg). The desired product (118 mg) was obtained.

NMR (C DC I ₃ ) δ value: 0.96 (3 Η, t, J = 7.3 Hz), 1.6 1-1.77 (2 H, m), 2.78 (2 H, t, J = 7.6 Hz), 3.07 (3 H, s), 6.63 (1 H, s), 7.12 (1 H, d, J = 8.6 Hz), 7.29 (1 H, d, J = 2. OH z), 7.57- 7.68 (3 H, m), 8.14 (1 H, s)

Example 24

 1-one (2,3-dibenzoylbenzoyl) 1-5-methanesulfonyl 2-n-pulp

 The same operation as in Example 1 using the compound of Reference Example 8 (100.Omg). 2,3-difluroylbenzoyl chloride (148 mg) and 60% sodium hydride (25.Omg). To give the desired product (79 mg).

NMR (CDC I ₃ ) δ value: 0.95 (3 Η, t, J = 7.3 Hz), Ί. 62-1.76 (2 H, m), 2.78 (2 H, t, J = 7.6 Hz), 3.07 (3 H, s), 6.59 (1 H, s), 7.18 (1 H, d, J = 8.9 Hz), 7. 27-7.55 (3 H, m), 7.62 (1 H, d, J = 8.6 Hz), 8.1 1 (1 H, s)

Example 25

 1 1 (3.4 dicyclo mouth benzoyl) 1 5-methanesulfonyl 2-π-propyl pyrindole

 The same operation as in Example 1 was performed using the compound of Reference Example 8 (100 · Omg), 3,4-diclo-benzobenzoyl chloride (176 mg), and 60% sodium hydride (25.Omg). (161 mg).

NMR (CDC I ₃ ) <5 values: 0.96 (3 H, t, J = 7.3 Hz), 1.63—1.77 (2 H, m), 2.81 (2 H, t) , J = 7.6 Hz), 3.07 (3 H, s), 6.63 (1 H, s), 7.10 (1 H, d, J = 8.9 Hz), 7 50- 7.63 (3 H, m), 7.86 (1 H, d, J = 2.0 Hz), 8.14 (1 H, d, J = 1.7 Hz)

Example 26

 1-I (2-chloro-4,5-difluent benzoyl) 1-5-Methanesulfonyl 1 2-n-Provirindole

 The compound of Reference Example 8 (100. Omg), 2-chloro-4,5-difluorobenzoic acid and thionyl chloride obtained 2-chloro-4,5-difluroylbenzoyl chloride (1 77 mg) and 60% hydrogen The same operation as in Example 1 was performed using sodium chloride (25. Omg) to obtain the desired product (163 mg).

NMR (CDC I ₃ ) «5 values: 0.97 (3 H, t, J = 7.3 Hz), 1.68—1.79 (2 H, m), 2.70 (2 H, t, J = 7.6 Hz), 3.07 (3 H, s), 6.60 (1 H, s), 7.20 (1 H, d, J = 8.9 Hz),

7.33-7.48 (2 H, m), 7.65 (1 H, d d, J = 1.7 H z,

8.9 Hz), 8.10 (1 H, d, J = 1.7 Hz)

 Example 27

1- (丄 5-dibromobenzoyl) -1-5-methanesulfonyl 2-n-pro Pilindole

 The compound of Reference Example 8 (100.Omg), 3,5-dibromobenzoic acid, and 3,5-dibromobenzoyl chloride (250 mg) obtained from dichloride and 60% sodium hydride (25.Omg ) Was carried out in the same manner as in Example 1 to obtain the desired product (168 mg).

NM R (C DC I ₃ ) <5 values: 0.96 (3 H, t, J = 7.3 Hz), 1.62-1.77 (2 H, m), 2.77 (2 H , t, J = 7.6 Hz), 3.07 (3

H, s), 6.63 (1 H, s), 7.13 (1 H, d, J = 8.9 Hz), 7.64 (1 H, dd, J = 1.7 Hz) , 8.9 Hz), 7.77 (2 H, d, J = 1.7 Hz), 7.98 (1 H, dd, J = 1.7 Hz, 1.7 Hz), 8.14 (1 H, d, J = 1.7 H z)

Example 28

 1- (2,3,5-trichlorobenzoyl) 1 5-methanesulfonyl 2-n-Probiindole

 Perform the same operation as in Example 1 using the compound of Reference Example 8 (100.Omg). 2,3,5-triclomethylbenzoyl chloride (205 mg) and 60% sodium hydride (25.Omg). (18 Omg).

NMR (CDC I ₃ ) <5 values: 0.96 (3 H, t, J = 7.3 Hz), 1.69—1-79 (2 H, m), 2.67 (2 H, t, J = 7.6 Hz, 3.07 (3 H, s), 6.60 (1 H, s), 7.24 to 7.28 (1 H, m), 7.44 (1 H, d, J = 2.3 Hz, 7.67 (1 H, dd, J = 1.7 Hz, 8.9 Hz), 7.73 (1 H, d, J = 2.3 H) z), 8.10 (1 H, d, J =

I. 7 Hz)

Example 29

1- (2,4,6-trimethylbenzoyl) 1 5-methanesulfonyl 2-n-propylindole The compound of Reference Example 8 (100. Omg), 2,4,6-trimethylbenzoic acid, and 2,4,6-trimethylbenzoyl chloride obtained from sodium chloride (153 mg) and 60% The same operation as in Example 1 was performed using sodium hydride (25. Omg) to obtain the desired product (13 1 mg).

NMR (CDC I ₃ ) δ value: 0.99 (3 Η, t, J = 7.3 Hz), 1.68—1.82 (2 H, m), 2.10 (6 H, s), 2.38 (3 H, s), 2.83 (2 H, brs), 3.04 (3 H, s), 6.57 (1 H, s), 6.88 (1 H , brs), 6.96 (2 H, s), 7.52 (1 H, d, J = 8.9 Hz), 8.06 (1 H, d, J = 1.7 Hz)

Example 30

 1 1 (2, 6-benzoyl dicyclo) 1 5-methanesulfonyl 2- n-propyl pyrindole

 The same operation as in Example 1 was carried out using the compound of Reference Example 8 (100. Omg), 2,6-dichlorobenzobenzoyl chloride (176 mg), and 60% sodium hydride (25. Omg). (172 mg).

NM R (CDC I ₃ ) <5 value: 0.69-1.20 (3 H, m), 1.65-1.95 (2 H, m), 3.06 (3 H, s), 3.2 1 (2 H, brs), 6.61 -8.88 (7 H, m)

Example 3 1

 1 1 (4-Methoxy 3-Full-year robenzoyl) 1 5-Methanesulfonyl 2 1 π-Provirindole

Reference example To a solution of the compound obtained in Example 8 (40 Omg) in dimethylformamide (17 ml) was added sodium hydride (102 mg) at 0, and after 15 minutes, 4-methoxy-3-furosulfate was added. Benzoyl chloride (438 mg) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution is poured into a saturated aqueous ammonium chloride solution, extracted with toluene, washed with sodium hydrogen carbonate and brine, dried over magnesium sulfate, filtered, and concentrated. Was. The obtained residue was separated by silica gel column chromatography (form: chloroform: 50: 1) to obtain a colorless amorphous target product (499 mg, 79%).

NM R (CDC I ₃ ) <5 values: 0.95 (3 H, t, J = 7.3 Hz), 1.5—1.8 (2 H, m), 2.83 (2 H, t, J = 7.7 Hz, 3.07 (3 H, s), 4.01 (3 H, s), 6.60 (1 H, s), 7.0-7.2 (2 H, m), 7.4-7.7 (3 H, m), 8.14 (1 H, d, J = 1.9 Hz)

Reference example 10

 1- (benzenesulfonyl) -1-5-methylthioindole

 To a solution of 5-methylthioindole (4.10 g) in dimethylformamide (50 ml) was added 60% sodium hydride (1.51 g) under ice-cooling. After stirring the reaction mixture at the same temperature for 15 minutes, benzenesulfonyl chloride (6.66 g) was added, and the mixture was stirred at room temperature for 1 hour. Next, the reaction solution was poured into a saturated aqueous solution of ammonium chloride, and extracted with toluene. The toluene was washed with saturated aqueous sodium bicarbonate and saturated saline, washed with anhydrous magnesium sulfate, passed through, and concentrated. The obtained residue was subjected to silica gel column chromatography to obtain the desired product (6.30 g) using chloroform-n-hexane (1: 2) as an elution solvent.

NMR (CDC I ₃ ) <5 values: 2.49 (3 H, s), 6.59 (1 H, d, J = 3.5 Hz), 7.26 (1 H, dd, J = 1.6 Hz, 8.6 Hz, 7.3 5-7.60 (5 H, m), 7.28-7.60 (4 H, m), 7.86 (2 H, d , J = 7.6 Hz), 7.9 1 (1 H, d, J = 8.6 Hz)

Reference example 1 1

 1- (benzenesulfonyl) -1-5-methanesulfonylindole

The same operation as in Reference Example 2 was carried out using the compound of Reference Example 10 (30 Omg) and 70% metaclo-perbenzoic acid (48.8 mg) to obtain the desired product (296 mg). NMR (C DC I ₃ ) <5 values: 3.06 (3 H, s) 6.80 (1 H, d, J = 3.9 Hz), 7.43— 7.67 (3 H, m ), 7.74 (1H, d, J = 3.9Hz), 7.82-7.98 (3H, m), 8.13-8.25 (2H, m)

Reference example 1 2

 5 Methanesulfonyl indole

 Reference Example 11 The same operation as in Reference Example 3 was carried out using the compound of Example 11 (14 Omg) and a 1N aqueous solution of potassium hydroxide (828 I) to obtain the desired product (72. Omg). NMR (CDC I 3) δ value: 3.09 (33, s), 6.71 (1 H, s), 7.33-7.43 (1 H, m), 7.53 (1 H, d J = 8.6 H 2), 7.74 (1 H, dd, J = 1.6 Hz, 8.6 Hz) 8.30 (1 H, s), 8.60 (1 H, bs)

Example 32

 1-1- (4-bromobenzoyl) -1-5-methanesulfonylindole

 A sample of the tradition 1 2 compounds (69. Omg), 4 bromobenzoyl chloride (1 1

The same operation as in Example 1 was carried out using 6 mg) and 60% sodium hydride (71.4 mg) to obtain the desired product (71.4 mg).

NMR (C DC I ₃ ) δ value: 3.11 (3Η, s), 6.77 (1H, d, J = 3.8 Hz), 7.44 (1H, d, J = 3.8 Hz), 7.64 (2 H, d, J = 8.5 Hz), 7.73 (2 H, d, J = 8.5 Hz), 7.95 (1 H, dd, J = 1.7 Hz, 8.6 Hz), 8.26 (1 H, d, J = 1.7 Hz), 8.54 (1 H, d, J = 8.6 H z)

Reference Example 1 3

1- (benzenesulfonyl) -1-2-n-butyl-5-methylthioindole Example 1 A solution of the compound (50. Omg) in tetrahydrofuran (1 ml) in tetrahydrofuran (1 ml) under a nitrogen stream at 1-78 at n-butyllithium (1. 60M, n-hexane The solution, 1.75 ml) was added dropwise. After the reaction mixture was stirred at the same temperature for 15 minutes, hexamethylfanic acid triamide (59.I mg) was added, and the mixture was further stirred for 15 minutes. Then, n-butyl iodide (36.4 mg) was added, and the mixture was stirred at 178 ° C for 2 hours. The reaction solution was poured into a saturated aqueous solution of ammonium chloride, and extracted with ethyl acetate. The ethyl persulfate layer was washed with a saturated saline solution, dried over anhydrous magnesium sulfate, passed through, and crimped. Here, the obtained residual brew was subjected to preparative thin-layer silica gel chromatography, and the desired product (40.5 mg) was obtained using ethyl eluate-n-hexane (1: 4) as a developing solvent. Was.

NMR (C DC I ₃ ) <5 values: 0.95 (3 H, t, J = 7.2 Hz), 1.30—1.52 (2 H, m), 1.60-1.80 (2 H, m), 2.50 (3 H, s), 2.96 (2 H, t, J = 7.6 Hz), 6.32 (1 H, s), 7.20 ( 1 H, dd, J = 1.9 Hz, 8.6 Hz), 7.31 (1 H, s), 7.32-7.58 (3 H, m), 7.71 (2 H, d, J = 7.0 Hz), 8.08 (1 H, d, J = 8.6 Hz)

Reference example 1 4

 1 — (benzenesulfonyl) 1 2 — n-butyl-5-methanesulfonylindole

The same operation as in Reference Example 2 was carried out using the compound of Reference Example 13 (39. Omg) and 70% metaclo-perbenzoic acid (56. Omg) to obtain the desired product (34.3 mg). NMR (CDC I ₃ ) <5 values: 0.96 (3 H, t, J = 7.2 Hz), 1.34-1.54 (2 H, m), 1.63-1.80 ( 2H, m), 3.00 (2H, t, J = 7.4Hz), 3.08 (3H, s), 6.50 (1H, s), 7.37-7 .67 (3H, m), 7.75 (2H, d, J = 7.3Hz), 7.81 (1H, dd, J = 1.5Hz, 8.8Hz) , 8.05 (1 H, d, J = 1.5 Hz), 8.36 (1 H, d, J = 8.8 Hz)

Reference example 1 5 2-n-butyl-5-methanesulfonylindole

The same operation as in Reference Example 3 was carried out using the compound of Reference Example 14 (33. Omg) and a 1N aqueous solution of hydroxylic acid (126 ULI) to obtain the desired product (18.8 mg). NMR (CDC I ₃ ) <5 values: 0.96 (3 H, t, J = 7.2 Hz), 1.32-1.52 (2 H, m), 1.65-1.82 ( 2H, m), 2.79 (2 H, t, J = 7.6 Hz), 3.07 (3 H, s), 6.37 (1 H, s), 7.40 (1 H , D, J = 8.6 Hz), 7.65 (1 H, dd, J = 1.6 Hz, 8.6 Hz), 8.14 (1 H, s), 8.35 (1 H, bs)

Example 33

 2-n-butyl-1 (4-chlorobenzene) 5-5-methanesulfonyl indole

 Reference Example 15 Compound of 5 (1 6. Omg), 4 mono-benzobenzoyl chloride (1

The same operation as in Example 1 was performed using 6.7 mg) and 60% sodium hydride (3.8 mg) to obtain the desired product (18.8 mg).

NM R (C DC I ₃ ) <5 value: 0.89 (3 H, t, J = 7.3 Hz), 1.23—1.47 (2 H, m), 1-53- 1. 73 (2 H, m), 2.83 (2 H, t, J = 7.5 Hz), 3.06 (3 H, s), 6.61 (1 H, s), 7.0 6 (1 H, d, J = 8.8 Hz), 7.51 (2 H, d, J = 8.7 Hz),

7.58 (1H, dd, J = 1.9Hz, 8.8Hz), 7.68 (2H, d, J = 8.7Hz), 8.13 (1H, d , J = 1.9 Hz)

Reference Example 1 6

1- (benzenesulfonyl) -1-5-methylthio-1-n-pentylindole Reference Example 10 Compound (30 Omg), n-pentyl iodide (293 mg), n-butyllithium (1.561, η) —The same operation as in Reference Example 13 was performed using hexane solution, 949 I) and hexamethyltyl triamide (355 mg) to obtain the desired product (25 Omg). NR (CDC I ₃ ) <5 value: 0.83-1.00 (3 H, m), 1.25-1.50 (4 H, m), 1.63-1.83 (2 H, m m), 2.50 (3 H, s), 2.95 (2 H, t, J = 7.2 H 2), 6.32 (1 H, s), 7.20 (1 H, dd, J = 2.0 Hz, 8.8 Hz), 7.32 (1 H, d, J = 2. OH z), 7.33 (3 H, m), 7.67-7.78 ( 2 H, m), 8.08 (1 H, d, J = 8.8 Hz)

Reference Example 1 7

 1- (benzenesulfonyl) -1-5-methanesulfonyl 2-n-pentylindole

 The same operation as in Reference Example 2 was carried out using the compound of Reference Example 16 (22 Omg) and 70% metaclo-perbenzoic acid (271 mg) to obtain the desired product (2 14 mg).

NMR (CDC I ₃ ) <5 values: 0.83-1.03 (3 H, m), 1.23-1.54 (4 H, m), 1.63-1.87 (2 H , m), 3.00 (2 H, t, J = 7.7 Hz), 3.08 (3 H, s), 6.52 (1 H, s), 7.36-7.65 ( 3H, m), 7.68-7.88 (3H, m), 8.08 (1H, d, J = 2.0Hz), 8.36 (1H, d, J = 8 .8 Hz)

Reference Example 1 8

 5 Methanesulfonyl 2-π-pentylindole

 The same operation as in Reference Example 3 was carried out using the compound of Reference Example 17 (20 Omg) and a 1N aqueous solution of potassium hydroxide (740 I) to obtain the desired product (123 mg).

NMR (CDC I ₃ ) δ value: 0.82-1.02 (3 Η, m), 1.27-1.47 (4 H, m), 1.66-1.83 (2 H, m ), 2.79 (2Η, t, J = 7.6Η), 3.07 (3Η, s), 6.38 (1Η, s), 7.41 (1Η, d, J) = 8.6 Η ζ), 7.66 (1 Η, dd, J = 1.6 Η ,, 8.6 Η), 8.15 (1 Η, s), 8.24 (1 Η, bs)

Example 34 1 1 (4 1 benzoyl) 1 5-methanesulfonyl 2- n-pentylindole

 Reference Example 18 The same operation as in Example 1 was carried out using the compound of Example 8 (10 Omg), benzoyl chloride (99.1 mg) and 60% sodium hydride (22.6 mg). (126 mg) was obtained.

NM R (C DC I ₃ ) δ value: 0.78-0.99 (3 Η, m), 1.19- 1.46 (4 H, m), 1.50- 1.80 (2 H, m), 2.82 (2 H, t, J = 7.6 Hz), 3.06 (3 H, s), 6.60 (1 H, s), 7.05 (1 H, d, J = 8.8 Hz), 7.5 1 (2 H, d, J = 8.6 Hz), 7.58 (1 H, dd, J = 1.6 Hz, 8.8 Hz), 7.68 (2 H, d, J = 8.6 Hz), 8.13 (1 H, d, J = 1.6 Hz)

Reference Example 1 9

 T- (benzenesulfinyl) -1-2-η-hexyl 5-methylthioindole Reference Example 10 Compound (30 Omg), iodide-π-hexyl (3 14 mg), n-butyltylium (1. The same operation as in Reference Example 13 was carried out using 56 M, n-hexane solution, 949 I) and hexamethylethyl triamide (355 mg) to obtain the desired product (296 mg).

NMR (CDC I ₃ ) value: 0.80-1.00 (3 H, m), 1.18-1.48 (6 H, m), 1, 62-1.80 (2 H, m m), 2.50 (3 H, s), 2.95 (2 H, t, J = 7.4 Hz), 6.32 (1 H, s), 7.20 (1 H, dd, J = 1.8 Hz, 8.9 Hz), 7.32 (1 H, d, J = 1.8 Hz), 7.35-7.60 (3 H, m), 7.71 (1 H, d, J = 7.OHz), 8.08 (1 H, d, J = 8.9 Hz)

Reference Example 20

1- (benzenesulfonyl) 1- 2-n-hexyl 5-methanesulfonylindole The same procedure as in Reference Example 2 was carried out using the compound of Reference Example 19 (27 Omg) and 70% metaclo-perbenzoic acid (353 mg) to obtain the desired product (234 mg).

NM R (CDC I ₃ ) δ · · 0.80-1.00 (33, m), 1.23-1.50 (6H, m), 1.67-1.8 3 (2H, m), 3.00 (2H, t, J = 7.6Hz), 3.08 (3H, s), 6.50 (1H, s), 7.38- 7.66 (3H, m), 7.75 (1H, d, J = 7.3Hz), 7.80 (1H, dd, J = 2.1Hz, 8.9 H z), 8.05 (1 H, d, J = 2.1 Hz), 8.36 (1 H, d, J = 8.9 Hz)

Reference Example 2 1

 2-n-hexyl 5-methanesulfonylindole

 The same operation as in Reference Example 3 was performed using the compound of Reference Example 20 (200 mg) and a 1 N aqueous solution of potassium hydroxide (71 δμ.I) to obtain the desired product (132 mg).

NMR (CDC I ₃ ) Mg: 0.82—1.36 (3 H, m), 1.22-1.5

2 (6 H, m), 1.6 2-1.87 (2 H, m), 2.79 (2 H, t, J = 7.6 Hz), 3.07 (3 H , S), 6.37 (1 H, s), 7.41 (1 H, d, J = 8.4 Hz), 7.64 (1 H, dd, J = 1.8 H z, 8.4 Hz), 8.15 (1 H, s), 8.43 (1 H, bs)

Example 3 5

 1 1 (4,1 benzoyl) 1 2—n—Hexyl 5—Methanesulfonylindole

 Reference Example 21 The same procedure as in Example 1 was carried out using the compound O 0 Omg of 1), benzoyl chloride (94.Omg) and 60% sodium hydride (21.5 mg). (11 Omg) was obtained.

NMR (CDC I ₃ ) <5 values: 0.77-1.00 (3 H, m), 1.13—1.4

3 (6 H, m), 1.52-1.76 (2 H, m), 2.82 (2 H, t, J = 7.6 Hz), 3.06 (3 H, m s), 6.60 (1 H, s), 7.06 (1 H, d, J = 8.8 Hz), 7.51 (2 H, d, J = 8.5 Hz), 7.61 (1 H, dd, J = 1.7 Hz, 8. 8 H z), 7.68 (2 H, d, J = 8.

5 Hz), 8.13 (1 H, d, J = 1.7 Hz)

Reference Example 22

 1- (benzenesulfonyl) -1-2-cyclopropylmethyl-5-methylthioindole

 Using the compound of Reference Example 10 (300 mg), cyclopropylmethyl bromide (200 mg), n-butyllithium (1.56 M, n-hexane solution, 949 ^ 1), and hexamethylphosphoric triamide (355 mg) The same operation as in Reference Example 13 was performed to obtain the desired product (84.8 mg).

NR (C DC I ₃ ) <5 value: 0.17-0.30 (2H, m), 0.46-0.69 (2H, m), 1.04-1.21 (1H , M), 2.50 (3 H, s), 2.87 (2 H, d, J = 6.8 Hz), 6.56 (1 H, s), 7.20 (1 H, dd , J = 1.9 Hz, 8.9 Hz), 7.28-7.60 (4 H, m), 7.71 (2 H, d, J = 7.3 Hz), 8.08 (1 H, d, J = 8.9 Hz)

Reference Example 23

 1- (benzenesulfonyl) -1-2-cyclopropylmethyl-5-methanesulfonylindole

 The same operation as in Reference Example 2 was carried out using the compound of Reference Example 22 (11 Omg) and 70% metaclo-perbenzoic acid (156 mg) to obtain the desired product (84.8 mg).

NMR (CDC I ₃ ) <5 values: 0.18-0.34 (2 H, m), 0.60-0. 73 (2 H, m), 1.05-1.23 (1 H, m), 2.92 (2 H, d, J = 6.5 Hz), 3.08 (3 H, s), 6.75 (1 H, s), 7.40-7.

67 (3 H, m), 7.75 (2 H, d, J = 7.6 Hz), 7.81 (1 H, dd, J = 1.8 Hz, 8.9 Hz), 8 .08 (1 H, s), 8.15 (1 H, d, J = 1.6 Hz), 8.35 (1 H, d, J = 8.9 Hz) Reference example 24

 2-cyclopropylmethyl-5-methanesulfonylindole

 The same operation as in Reference Example 3 was carried out using the compound of Reference Example 23 (8 Omg) and a 1 N aqueous solution of potassium hydroxide (308 I) to obtain the desired product (36.3 mg).

NM R (C DC I ₃ ) <5 values: 0.24-0.42 (2 H, m), 0.60-0.75 (2 H, m), 1.02-1.20 (1 H, m), 2.73 (2 Η, d, J = 6.8 Hz), 3.07 (3 H, s), 6.45 (1 H, s), 7.43 (1 H, d , J = 8.5 Hz), 7.67 (1 H, dd, J = 1.8 Hz, 8.5 Hz), 8.16 (1 H, s), 8.43 (1 H, bs)

Example 36

 1 1- (4-chlorobenzoyl) -2-cyclopropylmethyl-5-methanesulfonylindole

 The same procedure as in Example 1 was carried out using the compound of Reference Example 24 (33.Omg), 4-benzobenzoyl chloride (34.7 mg) and 60% sodium hydride (7.9 mg), and the target compound was obtained. (42.2 mg) was obtained.

NMR (CDC I ₃ ) <5 values: 0.13-0.36 (2 H, m), 0.50-0.70 (2 H, m), 0.94-1.17 ( 1 H, m), 2.76 (2 H, d, J = 6.8 Hz), 3.06 (3 H, s), 6.79 (1 H, s), 7.01 (1 H , d, J = 8.8 Hz), 7.5 1 (2 H, d, J = 8.4 Hz), 7.58 (1 H, dd, J = 1.7 Hz, 8. 8H z), 7.69 (2 H, d, J = 8.4 H z), 8.15 (1 H, d, J = 1.7 H z)

Reference Example 25

 2-aryl-1 11- (benzenesulfonyl) -5-methylthioindole

Reference Example 10 Compound (30 Omg), Aryl Oxide (183 mg), n-Butyl Lithium (1.56 M, n-Hexane Solution, 949 μI), Hexamethyldiacid The same operation as in Reference Example 13 was carried out using liamide (355 mg) to obtain the desired product (2 17 mg).

NR (C DC I ₃ ) 5 values: 2.49 (3 H, s), 3.74 (2 H, d, J =

6.5 Hz), 5.09-5.33 (2 H, m), 6.02-6. 12 (1 H, m), 6.34 (1 H, s), 7.21 ( 1 H, dd, J = 1.7 Hz, 8.6 Hz), 7.32 (1 H, d, J = 1.7 Hz), 7.34-7. 6 1 (3 H, m), 7.74 (2 H, d, J = 7.0 Hz), 8.07 (1 H, d, J = 8.6 Hz)

Reference Example 26

 2-aryl-1- (benzenesulfonyl) -5-methanesulfonylindole The same operation as in Reference Example 2 was carried out using the compound of Reference Example 25 (100 mg) and 70% metaclo-perbenzoic acid (143 mg). The desired product (106 mg) was obtained.

NM R (CDC I ₃ ) <5 values: 3.08 (3 H, s), 3.79 (2 H, d, J = 8.2 Hz), 5.1 0-5.39 (2 H , m), 5.88-6. 14 (1 H, m), 6.52 (1 H, s), 7.35-7.68 (3 H, m), 7.70-

7.95 (3 H, m), 8.06 (1 H, d, J = 1.8 Hz), 8.35 (1 H, d, J = 9.0 Hz)

Reference Example 27

 2-aryl-5-methanesulfonylindole

The same operation as in Reference Example 3 was carried out using the compound of Reference Example 26 (90 mg) and a 1 N aqueous solution of potassium hydroxide (360 MI) to obtain the desired product (46.5 mg). NMR (CDC I ₃ ) (5 values: 3.07 (3 H, s), 3.58 (2 H, d, J = 6.2 Hz), 5.20- 5.37 (2 H, m ), 5.92-6. 1 2 (1 H, m), 6.42 (1 H, s), 7.42 (1 H, d, J = 8.7 Hz), 7.66 ( 1 H, dd, J = 1.5 Hz, 8.7 Hz, 8.16 (1 H, s), 8.37 (1 H, bs) Example 37

 2-aryl-1- (4-chlorobenzoyl) -1-5-methanesulfonylindole Reference compound 27 (40.Omg), 4-chlorobenzoyl chloride (44.6 mg) and 60% hydrogenation The same operation as in Example 1 was performed using sodium (10.2 mg) to obtain the desired product (38.7 mg).

NMR (C DC I ₃ ) δ value-. 3.06 (3 Η, s), 3.63 (2 H, d, J = 6.2 Hz), 5.00—5.20 (2 H, m), 5.80-6.01 (1H, m), 6.64 (1H, s), 7.05 (1H, d, J = 8.9Hz), 7.51 ( 2 H, d, J = 8.4 Hz), 7.60 (1 H, dd, J = 1.5 Hz, 8.9 Hz), 7.67 (2 H, d, J = 8 H z), 8.14 (1 H, d, J = 1.5 Hz)

Reference Example 28

 5-ethylthioindole

 Under ice-cooling in a solution of 35% potassium hydride (584 mg) in tetrahydrofuran (1 Oml) under ice-cooling

(10 ml) was added. The reaction mixture was stirred at the same temperature for 15 minutes, cooled to 178 ° C., and t-butyllithium (1.46, n-pentane solution, 6.99 ml) was added. After stirring at the same temperature for 15 minutes, getyl disulphide (1.3 m

I) was added, and the mixture was further stirred at the same temperature for 30 minutes. Next, the reaction mixture was poured into a 1 N aqueous solution of sodium hydroxide, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The obtained residue was subjected to silica gel column chromatography, and the desired product (0.42 g) was obtained using n-hexane monoethyl ester (10: 1) as an elution solvent.

NMR (CDC I ₃ ) 5 values: 1.27 (3H, t, J = 7.26 Hz), 2.90 (2H, q, J = 7.26 Hz), 6.51 (1 H, s), 7.35-7.20 (3 H, m), 7.74 (1 H, s), 8.13 (1 H, brs), 7.74 (1 H, s)

Reference Example 29

 1-benzenesulfonyl 5-ethylthioindole

 Using the compound of Reference Example 28 (0.42 g), benzenesulfonyl chloride (424 I) and 60% sodium hydride (133 mg), the same operation as in Reference Example 10 was carried out to obtain the target compound (0.71 g). ).

NR (CDC I ₃ ) <5 values: 1.27 (3 H, t, J = 7.26 Hz), 2.92 (2 H, q, J = 7.26 Hz), 6.60 ( 1 H, d, J = 3.63 Hz), 7.3 1-7.34 (1 H, m), 7.41-7.56 (5 H, m), 7.85 1 7. 92 (3 H, m)

Reference Example 30

 1-benzenesulfonyl 5-ethylethyl 2-n-propylindole Reference Example 29 Compound 1 (0.61 g), n-butyllithium (1.60 M, n-hexane solution, 1.44 ml) The same procedure as in Reference Example 13 was carried out using hexamethylaliphatic triamide (669 / xI) and π-propyl iodide (374 μI) to obtain the desired product (214 mg).

NR (C DC I ₃ ) <5 values: 1.02 (3 H, t, J = 7.26 Hz), 1.28 (3 H, t, J = 7.26 Hz), 1.72 -1.81 (2 H, m), 2.88-2.96 (4 H, m), 6.33 (1 H, m), 7.15-7.30 (1 H, m), 7.32-7.1 (3H, m), 7.45-7.52 (1 H, m), 7.72 (2 H, d, J = 7.26 Hz), 8.08 (1 H, d, J = 8.57 Hz)

Reference example 3 1

1-benzenesulfonyl 5-ethaneethanesulfonyl-2-n-propylindole The same operation as in Reference Example 2 was carried out using the compound of Reference Example 30 (214 mg) and 70% metacro-perbenzoic acid (294 mg) to obtain the desired product (190 mg).

NM R (CDC I ₃ ) <5 values: 1.04 (3 H, t, J = 7.26 Hz), 1.28 (3 H, t, J = 7.26 Hz), 1.83 -1.75 (2 H, m), 2.99 (2 H, t, J = 7.26 Hz), 3.14 (2 H, q, J = 7.26 Hz), 6. 50 (1 H, s), 7.49-7.43 (2 H, m), 7.61 -7.56 (1 H, m), 7.78-7.74 (3 H, m), 8.01 (1 H, d, J = 1.32 Hz), 8.35 (1 H, d, J = 8.91 Hz)

Reference Example 32

 5-ethanesulfonyl 2-n-propylindole

 The same operation as in Reference Example 3 was carried out using the compound (19 Omg) of Reference Example 31 and a 1 N aqueous solution of potassium hydroxide (1.5 ml) to obtain the desired product (108 mg).

NMR (CDC I ₃ ) <5 values: Ί .02 (3 H, t, J = 7.59 Hz), 1.26 (3 H, t, J = 7.59 Hz), 1.82- 1.73 (2 H, m), 2.77 (2 H, t, J = 7.59 Hz), 3.13 (2 H, q, J = 7.26 Hz),

6.37 (1 H, s), 7.40 (1 H, d, J = 8.57 H 2), 7.60 (1 H, dd, J = 1.60 Hz, 8.58 Hz) ), 8.10 (1 H, s),

8.37 (1 H, b r s)

Example 38

 1-(4 benzoyl) 1-5-ethanesulfonyl 2- n-propylindole

 The same operation as in Example 1 was carried out using the compound of Reference Example 32 (108 mg), 4-chlorobenzoyl chloride (82 tI), and 60% sodium hydride (21 mg) to obtain the target compound ( 1 45 mg).

NMR (CDC I ₃ ) <5 values: 0.95 (3 H, t, J = 7.26 H 2), 1.27 (3 Η, t, J = 7.26 Η ζ), 1.75— 1.60 (2 Η, m), 2.8 1 (2 H, t, J = 7.26 H 2), 3.12 (2 H, q, J = 7.58 H z),

6.60 (1 H, s), 7.06 (1 H, d, J = 8.9 1 Hz), 7.56

7.43 (3 H, m), 7.68 (2 H, d, J = 8.25 Hz), 8.09 (1 H, d, J = 1.32 Hz)

Reference Example 33

 5— n-propyl

 5-Promoindole (2.0 g), 35% potassium hydride (1.17 g), t-butyllithium (1.6 M, n-pentane solution, 14.Oml), di (n-propyl The same operation as in Reference Example 28 was performed using disulphide (3.2 ml) to obtain the desired product (1.78 g).

NM R (CDC I ₃ ) δ value: 0, 99 (3 Η, t, J = 7.26 Hz), 1.69-1.55 (2 H, m), 2.86 (2 H, t , J = 7.26 Hz), 6.51 (1 H, s), 7.30-7.15 (3 H, m), 7.73 (1 H, s), 8.10 (1 H, brs)

Reference example 34

 1-benzenesulfonyl 5-n-propylthioindole

 Using the compound of Reference Example 33 (1.78 g), benzenesulfonyl chloride (1.67 ml) and 60% sodium hydride (522 mg), the same operation as in Reference Example 10 was carried out to obtain the target compound (3.08). g) was obtained.

NM R (CDC I ₃ ) <5 values: 1.00 (3 H, t, J = 7.25 Hz), 1.71-1.55 (2 H, m), 2.87 (3 H , T, J = 7.26 Hz), 6.60 (1H, d, J = 3.63 Hz), 7.32 (1H, dd, J = 8.58 Hz, 1.65 Hz), 7.57-7. 4 1 (5 H, m), 7.92-7.85 (3 H, m)

Reference Example 35

1-benzenesulfonyl 5--n-propylthio-2--π-propylindole Compound of Reference Example 34 (3.08 g), π-butyllithium (1.60Μ, η-hexane solution, 7.Oml). Hexamethyltrioxytriamide (3.2mI), oxalic acid n The same operation as in Reference Example 13 was performed using —propyl (1.8 ml) to obtain the desired product (1.24 g).

NMR (CDC I ₃ ) <5 values: 1.04-0.92 (6 H, m), 1.65-1.57 (2 H, m), 1.81-1.68 (2 H , m), 2.96-2.85 (4 H, m), 6.32 (1 H, s), 7.28-7.24 (1 H, m), 7.42-7.35 ( 3 H, m), 7.55-7.44 (1 H, m), 7.72 (2 H, d, J = 7.26 Hz), 8.07 (1 H, d, J = 8 . 58 Hz)

Reference Example 36

 1-benzenesulfonyl 5-n-propanesulfonyl 2-n-propylindole

 The same operation as in Reference Example 2 was carried out using the compound of Reference Example 35 (30 Omg) and 70% metacloperbenzoic acid (397 mg) to obtain the desired product (306 mg).

NMR (CDC I ₃ ) <5 values: 1.06-0.96 (6 H, m), 1.83-1.70 (4 H, m), 2.98 (2 H, t, J = 7.58 Hz,) 3.12-3.06 (2 H, m), 6.50 (1 H, s), 7.46-7.38 (2 H, m), 7. 60- 7.52 (1 H, m), 7.77-7.68 (3 H, m), 8.00 (1 H, s), 8.34 (1 H, d, J = 8.9 1 Hz)

Reference Example 37

 5-n-propanesulfonyl 2-n-propylindole

 The same operation as in Reference Example 3 was carried out using the compound of Reference Example 36 (306 mg) and an "I normal aqueous potassium hydroxide solution (3.0 mI)" to obtain the desired product (11 Omg).

NM R (CDC I ₃ ) <5 values: 1.02—0.92 (6 H, m), 1.80-1.70 (4 H, m), 2.77 (2 H,, J = 7.33 Η ζ), 3. 1 3-3. 0 4 (2 H, m), 637 (1 H, s), 7.40 (1 H, d, J = 8.55 Hz), 7.61 (1 H, dd, J = 1.7 1 H 2, 8.54 Hz), 8.10 (1 H, d, J = 0.98 Hz), 8.31 (1 H, brs)

Example 39

 Ί-1 (4,1 benzoyl) 1 5— π—Propanesulfonyl 2-n-Propyindole

 The same operation as in Example 1 was carried out using the compound of Reference Example 37 (11 Omg), benzoyl chloride (80 μI) and 60% sodium hydride (2 Omg), and the target compound (1 17 mg).

NMR (C DC I ₃ ) <5 values: 1.02-0.92 (6H, m), 1.76-1.62 (4H, m), 2.81 (2H, t, J = 7.57 Hz), 6.61 (1H, s), 3.15-3.03 (2H, m), 7.06 (1H, d, J = 8.54Hz) ), 7.57-7.45 (3 H, m), 7.76-7.66 (3 H, m), 8.09 (1 H, d, J = 1.46 Hz)

Reference Example 38

 1-(1-benzenesulfonyl 5-methylthioindole 2-^ r) — 1-cyclohexanol

N-Butyllithium (1.56 M, hexane solution, 76 1 μI) was added dropwise to a solution of diisopropylamine (132 mg) in tetrahydrofuran (0.75 mI) at 0, and the solution was distorted. At the same temperature, a tetrahydrofuran solution (1.25 ml) of 1-benzenesulfonylmethylthioindole (30 Omg) was added dropwise, and the reaction solution was stirred for 30 minutes. Further, the reaction solution was cooled to 178, cyclohexanone (117 mg) was added, the temperature was gradually raised to room temperature while stirring, and the mixture was further stirred for 3 hours. The reaction solution was poured into a saturated aqueous solution of ammonium chloride, extracted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, concentrated and concentrated. The obtained residue was recrystallized from chloroform-hexane to give the target compound as a colorless needle (268 mg, 68%).

NR (CDC I ₃ ) δ value: 1.1-1. (1 H, m), 1.5—1.8 (5 H, m), 1.8-2.0 (3 H, m), 2.3—2.6 (1 H, m), 2.45 (3 H, s), 4.66 (1 H, s), 6.65 (1 H, s), 7.14 ( 1 H, dd, J = 2.1 Hz, 8.8 Hz), 7.28 (1 H, d, J = 2.1 Hz), 7.3-7.6 (3 H, m ), 7.80 (2 H, d, J = 7.6 Hz),

7.89 (1 H, d, J = 8.8 Hz)

E I-S m / z: 401 (M +)

Reference example 39

 1-benzenesulfonyl 5-methylthio-2- (cyclohexene 1 1 ^ r) 1 indole

 A toluene solution (40 ml) of the compound of Reference Example 38 (1.6 g) and toluene sulfonic acid (69 mg) was passed for 1 hour, and the solution was poured into a saturated aqueous solution of ammonium chloride to separate toluene II. The layer was washed with brine, dried over magnesium sulfate, passed, and concentrated, and the resulting residue was separated by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to give a colorless oil. The desired product (1.4 g, 92) was obtained.

NMR (CDC I ₃ ) «5 values: 1.6-1.9 (4 H, m), 2.1-2.6 (4 H, m), 2.47 (3 H, s), 5. 72 (1H, m), 6.27 (1H, s), 7.1-7.5 (5H, m), 7.60 (2H, d, J = 7.0Hz),

8.08 (1 H, d, J = 8.9 Hz)

Reference example 40

 1-Benzenesulfonyl 5--Methanesul-tree 2- (cyclohexene-1-yl) 1-indole

To a solution of the compound of Reference Example 39 (18 Omg) in chloroform (4.7 ml) was added, at 0, methacloperbenzoic acid (232 mg) and the mixture was stirred at the same temperature for 30 minutes. Next Then, the reaction solution was poured into a saturated aqueous solution of sodium hydrogen carbonate and extracted with a black hole form. The formal layer was washed with brine, dried over magnesium sulfate, concentrated and concentrated. The resulting residue was separated using silica gel column chromatography (form: methanol = 50: 1) to give the desired product as a white powder (174 mg, 90%).

NR (C DC I ₃ ) value: 1.6-1.9 (4 H, m), 2.2 1 (2 H, m), 2.39 (2 H, m), 3.07 (3 Η , S), 5.7 1 (1 H, m),

6.46 (1 Η, s), 7.37 (2 Η, t, J = 7.8 Η ζ), 7.52 (1 Η, t, J = 7.8 Η ζ), 7.65 ( 2 Η, d, J = 7.6 Η ζ), 7.83

(1 Η, dd, J = 1.2 Η ζ, 8.9 ζ ζ), 8.02 (1 Η, d, J = 1.2 Η ζ), 8.91 (1 Η, d, J = 8. 9 Η ζ)

Reference example 4 1

 5-Methanesulfonyl 2- (cyclohexene-11-yl) -indole 1N solution of the compound of Reference Example 40 (150 mg) in methanol (3.6 mI) (1N potassium hydroxide solution (722 ^ 1) ) And refluxed for 4 hours. Then, the reaction solution was concentrated, poured into water, and extracted with black form. The port-form layer was washed with brine, dried over magnesium sulfate, filtered and concentrated. The obtained residue was refined using silica gel column chromatography (chloroform: methanol = 20: 1) to obtain the desired product as a white powder (75 mg, 76%).

NMR (CDC I ₃ ) <5 values: 1.6-1.9 (4 H, m), 2.17 (2 H, m), 2.46 (2 H, m), 3.07 ( 3Η, s), 6.23 (1Η, bs), 6.54 (1H, s), 7.42 (1H, d, J = 8.6Hz),

7.67 (1 H, d d, J = 1.8 Hz, 8.6 Hz), 8.17 (1 H, s), 8.50 (1 H, b s)

 Example 40

1-(4-fluorobenzoyl) 1-5-methanesulfonyl 2--(cyclohexyl) (Sen-ichi)

 Reference Example 4 Sodium hydride (11 mg) was added to a dimethylformamide solution (1.8 ml) of the compound (5 Omg) of 1 at 0 * C, and the mixture was stirred at the same temperature for 15 minutes. One-year-old robenzoyl chloride (43 mg) was added, and the mixture was stirred at room temperature overnight. The reaction solution was poured into a saturated aqueous solution of ammonium chloride and extracted with toluene. The toluene layer was washed with saline, dried over magnesium sulfate, concentrated and concentrated. The obtained residue is thin-layer chromatography on silica gel (form: methanol = 50:

1. Next, hexane: ethyl ethyl ester = 1: 1) was used to separate the desired product into a white powder.

 (21 g, 30%) was obtained.

NMR (CDC I ₃ ) «5 values: 1.2—1.5 (4H, m), 1.90 (2 H, m), 2.11 (2 H, m), 3.09 (3 H, s), 5.76 (1H, m), 6.64 (1H, s), 7.12 (2H, t, J = 8.5Hz), 7.59 (2H , M), 7.79 (1 H, dd, J = 1.8 Hz, 8.64 Hz), 7.94 (1 H, d, J = 8.6 Hz), 8.20 ( (1 H, d, J = 1.8 Hz) Reference example 42

 1-benzenesulfonyl 2-tributylstannyl 5-methylthioindole

)

1 To a solution of 5-benzenethiosulfonyl 5-methylthioindole (1. Og) in tetrahydrofuran (3 OmI) at 178 ° C at n-butyllithium (1.6 M, hexane solution, 2. 5 ml) was added dropwise. After 15 minutes, hexamethylphosphate triamide (1.2 g) was added. After another 15 minutes, tributyltin chloride (1.34 g) was added. Stirred for 90 minutes. Then, the mixture was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. ft The ethyl acetate was washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and concentrated. The obtained remaining brew was separated by silica gel column chromatography (hexane: ethyl ethyl acetate = 10: 1) to obtain a colorless oily target product (1.46 g, 75%). NMR (CDC I ₃ ) <5 僱: 0.89 (9H, t, J = 7.2Hz), 1.0-1.7 (18H, m), 2.48 (3H , S), 6.75 (1H, s), 7.13 (1H, d, J = 8.8H2), 7.3—7.6 (3H, m), 7. 6 2 (2 H, d, J = 7.0 Hz), 7.73 (1 H, d, J = 8.8 Hz)

Reference example 4 3

 1-benzenesulfonyl 2-phenyl-5-methylthioindole

 An ethanol suspension (12 ml) of the compound of Reference Example 42 (120 mg), benzene iodide (700 mg) and dichloromethane palladium bistriphenylphosphine (133 mg) was passed through for 3 days. The reaction solution was filtered using a ceramic, and the resulting liquid was reduced. The residue was separated by silica gel thin-layer chromatography (hexane: ethyl ethyl sulphate = 10: 1) to give the target compound (99 g, 50%) as a colorless oil.

NMR (CDC I ₃ ) <5 values: 2.5 1 (3 H, s), 6.48 (1 H, s), 7.

2—7.6 (1 2 m, m), 8.2 2 (1 H, d, J = 8.6 H z)

Reference example 44

 1-benzenesulfonyl 2-phenyl-5-methanesulfonylindole Using the compound of Reference Example 43 (90 mg) and in the same manner as in Example 3, the target compound as a colorless amorphous (85 mg, 87%) I got

NMR (CDC I ₃ ) δ value '· 3.10 (3 Η, s), 6.64 (1 H, s), 7.2-7.6 (1 OH, m), 7.91 (1H, dd, J = 1.6Hz, 7.3H2), 8.11 (1H, d, J = 1.6H2), 8.52 (1H, d, J = 7.

3 Hz)

Reference example 4 5

 2-Feuniru 5-Methanesulfonylindole

 Using the compound of Reference Example 44 (8 Omg), the desired product (49 mg, 99%) as a white powder was obtained in the same manner as in Example 4.

NMR (CDC IJ <5 value: 3.10 (3 H _? S), 6.94 (1 H, s), 7. 3-7. 6 (4 H, m), 7.6—7.8 (3 H, m), 8.26 (1 H, s), 8.75 (1 H, bs)

Example 41

 1- (4,1-dichlorobenzene) 1-5-Methanesulfonyl 2-phenylphenyl

 Using the compound of Reference Example 45 (40 mg) and 4-monobenzoyl chloride (39 mg), a colorless amorphous target product (24 mg, 40%) was obtained in the same manner as in Example 5.

NMR (CDC I ₃ ) δ value: 3.12 (3Η, s), 6.89 (1H, s), 7.1-7.4 (7H, m), 7.51 (2H , d, J = 8.6 Hz), 7.84 (1 H, dd, J = 1.5 H2, 8.8 Hz), 7.92 (1 H, d, J = 8. 8 Hz), 8.29 (1 H, d, J = 1.5 Hz)

Reference Example 46

 2- (1-benzene-sulfur 2-chloro 5-methylthioindole-2-yl) isopropanol

 The desired product (2.4 g, 50%) as a white powder was obtained in the same manner as in Example 1 using acetone (767 mg).

NMR (CDC I ₃ ) <5 values: 1.84 (6 H, s), 2.46 (3 H, s), 4.94 (1 H, s), 6.65 (1 H, s), 7.15 (1 H, d, J = 8.8 Hz), 7.2-1.6 (4 H, m), 7.82 (2 H, d, J = 8. OH z), 7.89 (1 H, d, J = 8.8 H z)

E I-S m / z: 36 1 (+)

Reference Example 47

1 Benzenesulfonyl 2-isopropenyl 5-methylthioindole Using the compound (858 mg) of Reference Example 41, the target compound as a white powder (977 mg, 69%) in the same manner as in Example 2. I got NMR (CDC I ₃ ) <5 values: 2.24 (3 H, s), 2.48 (3 H, s),

5.14 (1 H, s), 5.29 (1 H, s), 6.37 (1 H, s), 7.2-7.5 (5 H, m), 7.65 (2 H, d, J = 7.6 Hz), 8.08 (1 H, d, J = 8.6 Hz)

Reference Example 48

 1-benzenesulfonyl 5-methanesulfonyl 2-isopropenylindole

 Using the compound of Reference Example 47 (825 mg), a colorless oily target compound (428 mg, 49%) was obtained in the same manner as in Reference Example 40.

NR (CDC I ₃ ) <5 values: 2.25 (3 H, s), 3.07 (3 H, s),

5.15 (1 H, s), 5.37 (1 H, s), 6.55 (1 H, s), 7.3-7.6 (3 H, m), 7.70 (2 H, d, J = 7.6 Hz), 7.85 (1 H, dd, J = 1.5 Hz, 8.6 Hz), 8.03 (1 H, d, J = 1. 5 Hz), 8.36 (1 H, d, J = 8.6 Hz)

Reference 49

 2-Isopropenyl-5-methanesulfonylindole

 Using the compound of Reference Example 48 (40 mg), the desired product (249 mg, 99%) as a white powder was obtained in the same manner as in Reference Example 41.

NMR (C DC I ₃ ) <5 values: 2.21 (3 H, s), 3.08 (3 H, s), 5.19 (1 H, s), 5.40 (1 H , s), 6.66 (1 H, s), 7.45 (1 H, d, J = 8.5 Hz), 7.71 (1 H, d, J = 8.5 Hz) ), 8.20 (1 H, s), 8.6 1 (1 H, bs)

Example 42

 1-(4 Benzoyl) 1-5-Methanesulfonyl 2-isoprobenyl indole

Using the compound of Reference Example 49 (23 Omg), a colorless solution was obtained in the same manner as in Example 5. The desired product of Rufus (173 mg, 47%) was obtained.

NMR (C DC I ₃ ) <5 values: 1.95 (3 H, s), 3.09 (3 H, s), 5.04 (1 H, s), 5.07 (1 07, s) ), 6.78 (1 1, s), 7.43

(2 Η, d, J = 8.4 Hz), 7.58 (2 H, d, J = 8.4 Hz), 7.78 (2 H, m), 8.23 (1 H, s)

Test example 1

 Preparation of COX-2 expressing cells

 Human COX-2 cDNA was recloned from the LPS-stimulated human monocyte cDNA library (CL ONET ECH) by plaque hybridization (p I aquehybridization), and pCOS-1 Into pCOS—hCOX-2. pCOs—hCOX-2 was transfected into CHO cells by electroporation to obtain a COX-2 expression clone 2A12.

 Test example 2

 C 0 X—2 activity measurement 沬

COX-2 expression clone 2 A12 was plated on a 96-well plate with 300 OZwe II, and after culturing for 48 hours, weII was washed with Hanks solution, and each compound dissolved in Hanks solution was added. And incubated at 37 ^eC for 30 minutes. The arachidonic acid solution was added to a final concentration of 10 M, and the mixture was further cultured for 30 minutes, and the amount of PGE 2 in the culture supernatant was measured using a PGE 2 ElA kit (CAYMAN). COX-2 activity (%) is measured by measuring the amount of PGE 2 in each we II, with the amount of PGE 2 produced in we II to which Hanks solution was added as 100%, and the IC50 value of each compound. Was calculated. Table 4 shows the results. Table 4 Compound No. C ₅₀ value (M) Example 2 4.0X 10 ^"7

Example 3 6.0 X 10 one ⁷

Example 4 4.0 X 10- ⁷

Industrial applicability

 The compound of the present invention has a CO X-2 inhibitory activity and the like, and is useful as a drug such as an anti-inflammatory drug.

Claims

Range of quest

1. General formula (1)

In the formula, R ¹ is a hydrogen atom, a linear or branched alkyl group having 7 to 7 carbon atoms, a linear or branched alkenyl group having 2 to 7 carbon atoms, and a straight-chain or branched alkenyl group having 2 to 7 carbon atoms. A chain or branched alkynyl group, a cycloalkenyl group having 4 to 6 carbon atoms, an aryl group, a heteroaryl group, an alkyl group in which the alkyl portion is a linear or branched alkyl group having 7 to 7 carbon atoms An alkenyl group in which the carbonyl group and the alkenyl moiety are linear or branched alkenyl groups having 2 to 7 carbon atoms, and a linear or branched alkynyl group in which the alkynyl moiety is 2 to 7 carbon atoms An alkynylcarbonyl group, or one (CH ₂ ) _m —R ⁴ ;

 Here, m represents an integer of 0 to 3, and represents a cycloalkyl group having 3 to 6 carbon atoms which may be substituted with a linear or branched alkyl group having 3 to 3 carbon atoms.

R ² an S 0 ₂ - represents an R ^5, wherein R ⁵ represents a straight-chain or branched alkyl group having 1 to 3 carbon atoms,

R ³ is an aryl group which may have a substituent, a cycloalkyl group having 3 to 6 carbon atoms which may have a substituent, or a monocyclic heterocyclic ring which may have a substituent Represents a group,

Or a hydrate thereof.

2. In the general formula (1), R ² is a methanesulfonyl group or an ethanesulfonyl group. 2. The compound according to claim 1, or a hydrate thereof.

3. In the general formula (1), R ¹ is a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched alkenyl group having 2 to 4 carbon atoms. Or an alkynyl group, a cycloalkenyl group having 4 to 6 carbon atoms, an aryl group, a heteroaryl group, wherein the alkyl portion is a straight-chain or branched alkyl group having 1 to 4 carbon atoms, and an alkylcarbonyl group and an alkenyl portion are carbon atoms. An alkenylcarbonyl group which is a linear or branched alkenyl group having 2 to 4 carbon atoms, an alkynylcarbonyl group whose alkynyl moiety is a linear or branched alkynyl group having 2 to 4 carbon atoms, or (CH ₂ ) _m -R \ wherein m and R ⁴ represent the same meaning as described above,

R ² is a methanesulfonyl group or an ethanesulfonyl group, and R ³ is a phenyl group which may have a substituent, a cycloalkyl group having 3 to 6 carbon atoms which may have a substituent, or a substituent Claims which is a simple Hunch type heterocyclic group which may have

2. The compound according to item 1, or a hydrate thereof.

4.2 2-Ethyru 1- (4-fluorobenzoyl) 1-5-Methanesulfonylindole,

 1- (4-fluorobenzoyl) 1-Methanesulfonyl 2-n-propylindole,

 1-1- (4-bromobenzoyl) -1-5-methanesulfonyl 2-n-propylindole,

 1- (4-methylbenzene) 1-Methanesulfonyl 2-n-propylindole,

 5-Methanesulfonyl 1-1 (4-methylbenzoyl) 1-2-n-propylindole,

5-Methanesulfonyl 2-n-propyl-1-1 (4-trimethyl romethylben Zyl) One indole,

 1 1 (4-benzobenzene) 1 5-methanesulfonyl 2-methylindole,

 5-Methanesul tree 2-l 1 (4-l-benzyl) 1 2-π-propylindole,

 1 1- (4-hydroxybenzoyl) 1-5-Methanesulfonyl- 2-π-propylindole,

 1-(2,4 dicyclobenzene) 1-5-Methanesulfonyl 2-n-propylindole,

 1- (5-bromo-2-furoyl) -1-5-methanesulfonyl 2-n-propylindole,

 5-Methanesulfonyl 11- (4-methoxybenzoyl) 1-2-n-propylindole,

 1-(6-nicotinol) 1 5-methanesulfonyl 2- n-propylindole,

 1- (4-Ethylbenzoyl) -1-5-Methanesulfonyl 2-n-propylindole,

 1 1 (5—Promo 2—Brozen Benzyl) 1 5—Methanesulfonyl 2—n—Provirindole,

 5-Methanesulfonyl 1 1 (4-methylthiobenzoyl) 1 2-n-propyl indole,

 1 1 (2,4,6-trichlorobenzoyl) 1 5-methanesulfonyl 2-n-propylindole,

 1 Benzoyl 5-methanesulfonyl 2-n-propylindole,

1- (4-Isopropylbenzoyl) -1-5-Methanesulfonyl 2-n-Propylindole, 1-cyclohexylcarbonyl 5-methanesulfonyl-2-pi-propylindole,

 1 (5-chloro-2-tenol) 1 5-methanesulfonyl 2-n-propyl indole,

 1- (4-n-propylbenzoyl) -1-5-methanesulfonyl 2-n-propylindole,

 1 1 (3,5-dichlorobenzene) — 5-methanesulfonyl 2-n-propylindole,

 1 1 (2,3-dibenzoylbenzoyl) 1 5-methanesulfonyl 2-n-propylindole,

 1 1 (3,4 dicyclobenzene) 1-5-Methanesulfonyl 2-n-propylindole,

 1 1 (2-Chloro-4,5-difluent benzoyl) — 5-Methanesulfonyl

2—n—Provir indole,

 1- (3,5-dibromobenzoyl) -1-5-methanesulfonyl 2-n-propylindole,

 1-(2,3,5-trichlorobenzoyl) 1 5-Methanesulfonyl 2-n-Provirindole,

 1 (2,4,6-trimethylbenzoyl) 1 5-methanesulfonyl 2-n-propylindole,

 1 1 (2,6-dichlorobenzene) 1 5-Methanesulfonyl 2-n-propylindole,

 1 1 (4-Methoxy 3—Venzoyl) 1 5—Methanesulfonyl 2-n—Provirindole,

 1- (4-bromobenzoyl) — 5-methanesulfonylindole,

2-n-Butyl-1 — (4-chlorobenzene) -5-Methanesulfonyl India Tool,

 1- (4-methylbenzene) 5--Methanesulfonyl 2-n-pentylindole,

 1 1 (4 1-opening benzoyl) 1 2-n-hexyl 5-methanesulfonyl indole,

 1 1- (4-chlorobenzoyl) 1-2-cyclopropylmethyl-5-methanesulfonylindole,

 2-Aryl-1-1 (4-methylbenzene) 5-5-Methanesulfonylindole,

 1 1 (4-methylbenzoyl) 1 5-ethanesulfonyl 2-n-propylindole,

 1-(4 benzoyl) 1 5-n-propane sulfonyl 2-π-propyl indole,

 1 1 (4 1-year-old benzoyl 5-5-methanesulfonyl 2- 2- (cyclohexene 1 1 1 ^ ^) 1 indole,

 1- (4-chlorobenzene) 1-Methanesulfonyl-2-phenylindole and

 1-1- (4-chlorobenzene) 1-5-Methanesulfonyl 2--2-T-soprobenylindole

2. The compound or a hydrate thereof according to claim 1, which is selected from the group consisting of:

5. General formula (2)

In the formula, each of 8 'and ² has the same meaning as defined in claim 1. Represents,

And a compound represented by the general formula (3)

R ³ C00H (3)

Wherein R ³ has the same meaning as defined in claim 1, and is reacted with a carboxylic acid represented by or a reactive derivative thereof. A method for producing a compound.

6. A pharmaceutical composition comprising the compound according to any one of Items 1 to 4 and an additive component.

7. A cyclooxygenase inhibitor comprising the compound according to any one of claims 1 to 4.

8. An anti-inflammatory agent comprising the compound according to any one of claims 1 to 4.