JP2006137723A - Sulfonamide derivatives - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sulfonamide derivative having a function regulating action of thymos and activation-regulated chemokine [TARC (CCL17)] and / or macrophage-delivered chemokine [MDC (CCL22)], or a pharmacologically acceptable thereof Providing salt.
SOLUTION: General formula (I)
[Chemical 6]

[Wherein R ¹ and R ² represent a hydrogen atom or the like,
(I) when R ¹ and R ² represent a hydrogen atom or the like,
Y represents alkylene, R ³ represents a substituted or unsubstituted bicyclic heterocyclic group, R ⁴ represents 2,3-dichlorophenyl,
(Ii) when R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocycle,
Y represents a substituted or unsubstituted alkylene, R ³ represents a hydrogen atom or the like, and R ⁴ represents a substituted or unsubstituted aryl or the like], or a pharmaceutically acceptable salt thereof. To do.
[Selection figure] None

Description

  The present invention is directed to the thymus and activation-regulated chemokine (TARC; CC chemokin ligand 17 (CCL17)) and / or the macrophage-activated chemokine (macroede chemokine; Chemokine ligand 22 (CCL22))], and sulfone useful for the treatment and / or prevention of various diseases involving T cells such as various inflammatory diseases (eg, allergic diseases, autoimmune diseases, etc.) The present invention relates to an amide derivative or a pharmacologically acceptable salt thereof.

  TARC is a T cell migration factor [Journal of Biological Chemistry, 271, p. 21514 (1996)], and MDC was discovered as a monocyte migration factor [Journal of Experimental Medicine, 185, p. 1595 (1997)]. In particular, TARC is produced from monocytes stimulated with T helper 2 [T Helper 2 (Th2)] cytokines, and is therefore assumed to be involved in allergic diseases [Journal of Biological Chemistry ( Journal of Biological Chemistry), 271, p. 21514 (1996)] and subsequent analysis have reported that both TARC and MDC are ligands for the C-C chemokine receptor 4 [C-C chemokine receptor 4 (CCR4)]. Biological of Chemistry, 272, p. 15036 (1997), Journal of Biological Chemistry, 273, p. 1764 (1998)].

  CCR4 has been cloned as a receptor expressed in T cells and thymocytes [Biochemical and Biophysical Research Communications, 218, p. 337 (1996)] and subsequent studies have reported that CCR4 is expressed primarily in T cells called the Th2 type [Journal of Experimental Medicine, 187]. Volume, p. 875 (1998), Journal of Immunology, 161, p. 5027 (1998)].

  It has also been reported that CCR4 antibody is effective in animal models of allergic diseases such as asthma. In addition, antibodies against TARC inhibit airway hypersensitivity in mice [Journal of Immunology, 166, p. 2055 (2001)] and antibodies against MDC inhibit eosinophil infiltration into alveoli in mice [Journal of Immunology, 163, p. 403 (1999)] has been reported.

On the other hand, a pyrazine derivative having an endothelin antagonism (see Patent Document 1) is known. In addition, N-pyrazinyl-2-thiophenesulfonamide derivatives (see Patent Document 2) and N-pyrazinylbenzenesulfonamide derivatives (see Patent Document 3) are known as therapeutic agents for diseases involving chemokines. Known chemokine receptor antagonists include N-pyrazinyl benzenesulfonamide derivatives, N- (2-quinoxalinyl) benzenesulfonamide derivatives, and the like (see Patent Document 4). Furthermore, pyridopyrazin-2-one-3-ylmethanesulfonamide derivatives (see Patent Document 5) are known.
Japanese National Patent Publication No. 9-510987 WO03 / 51870 pamphlet International Publication No. 03/59893 Pamphlet International Publication No. 04/07472 Pamphlet WO 97/32858 pamphlet

  An object of the present invention is to have a function-regulating action of TARC and / or MDC, for example, involving various T cells such as various inflammatory diseases (for example, allergic diseases, autoimmune diseases, etc.), rejection at the time of transplantation, etc. Disease [more specifically, asthma, rhinitis, allergic rhinitis, chronic rhinitis, hay fever, conjunctivitis, allergic conjunctivitis, urticaria, psoriasis, atopic dermatitis, cutaneous pruritus, cutaneous candidiasis, oral cavity Candidiasis, rheumatoid arthritis, various collagen diseases, systemic lupus erythematosus, Sjogren's syndrome, cell rejection during organ transplantation, cancer, malignant lymphoma, leukemia such as adult T-cell leukemia (ATL), eosinophilic pneumonia, eosinophils Sinusitis, eosinophilic polynasal rhinitis, interstitial cystitis, endometriosis, Churg-Strauss syndrome, sepsis, pain, neuralgia, insulin-dependent diabetes (ID) M), Mycosis fungoides, contact dermatitis, cutaneous T-cell lymphoma, airway hypersensitivity, atherosclerosis, contact hypersensitivity, myocardial infarction, angina, arterial restenosis, ischemia reperfusion , Stroke, systemic anaphylaxis, drug allergy, insect bite, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis (UC), ileitis, enteritis, vaginitis, eczema, vasculitis, spondyloarthritis, hard Sulfonamide derivatives useful for the treatment and / or prevention of dermatoses, multiple sclerosis, glomerulonephritis, osteoarthritis, chronic obstructive pulmonary disease (COPD), etc., suppression of cancer metastasis, etc. Is to provide a chemically acceptable salt.

The present invention relates to the following (1) to (16).
(1) General formula (I)

<In the formula, R ¹ and R ² are the same or different and each represents a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted Or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted lower alkoxy, -NR ^a R ^b ( In the formula, R ^a and R ^b are the same or different and each is a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted Or unsubstituted aryl, substituted or unsubstituted aliphatic heterocyclic group or substituted or unsubstituted Aromatic a heterocyclic group) or -COR ⁵ [wherein, ^{R 5} is hydroxy, substituted or unsubstituted lower alkoxy, substituted or unsubstituted ^aryloxy, in ^-NR aa ^{R bb (wherein, R aa} and R ^bb represents the same as R ^a and R ^b , respectively, and represents an aliphatic heterocyclic group or an aromatic heterocyclic group], or R ¹ and R ² together with adjacent carbon atoms. To form a substituted or unsubstituted aromatic heterocycle,
(I) R ¹ and R ² are the same or different and are a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or Unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted lower alkoxy, —NR ^a R ^b (formula Wherein R ^a and R ^b are as defined above) or —COR ⁵ (wherein R ⁵ is as defined above),
Y represents alkylene, R ³ represents a substituted or unsubstituted bicyclic heterocyclic group,
R ⁴ represents 2,3-dichlorophenyl,
(Ii) when R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocycle,
Y represents a substituted or unsubstituted alkylene, R ³ represents a hydrogen atom, a substituted or unsubstituted aryl, a substituted or unsubstituted aliphatic heterocyclic group or a substituted or unsubstituted aromatic heterocyclic group,
R ⁴ represents a substituted or unsubstituted aryl or a substituted or unsubstituted aromatic heterocyclic group>
Or a pharmacologically acceptable salt thereof.
(2) R ¹ and R ² are the same or different and are a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted C _1-10 alkyl, substituted or unsubstituted C _2-10 alkenyl, substituted or unsubstituted C _2-10 alkynyl, substituted or unsubstituted C _3-8 cycloalkyl, substituted or unsubstituted C _6-14 aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic ring A group, substituted or unsubstituted C _1-10 alkoxy, —NR ^c R ^d , wherein R ^c and R ^d are the same or different and each represents a hydrogen atom, substituted or unsubstituted C _1-10 alkyl, substituted or non-substituted Substituted C _2-10 alkenyl, substituted or unsubstituted C _2-10 alkynyl, substituted or unsubstituted C _3-8 cycloalkyl, substituted or unsubstituted _{C 6-14} aryl, in substituted or an unsubstituted aliphatic heterocyclic group or a substituted or unsubstituted aromatic heterocyclic group) or -COR ^{5A [wherein, R 5A} is hydroxy, substituted or unsubstituted C _1-10 alkoxy, substituted or unsubstituted C _6-14 aryloxy, —NR ^cc R ^dd (wherein R ^cc and R ^dd are as defined above for R ^c and R ^d ), an aliphatic heterocyclic group Or represents an aromatic heterocyclic group], or R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocyclic ring,
(I) R ¹ and R ² are the same or different and are a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted C _1-10 alkyl, substituted or unsubstituted C _2-10 alkenyl, substituted or unsubstituted C _2-10 alkynyl, substituted or unsubstituted C _3-8 cycloalkyl, substituted or unsubstituted C _6-14 aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic ring A group, substituted or unsubstituted C _1-10 alkoxy, —NR ^c R ^d (wherein R ^c and R ^d are as defined above) or —COR ^5A (wherein R ^5A is as defined above); Is)
Y represents C _1-10 alkylene, R ³ represents a substituted or unsubstituted bicyclic heterocyclic group,
R ⁴ represents 2,3-dichlorophenyl,
(Ii) when R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocycle,
Y represents a substituted or unsubstituted C _1-10 alkylene, R ³ represents a hydrogen atom, a substituted or unsubstituted C _6-14 aryl, a substituted or unsubstituted aliphatic heterocyclic group, or a substituted or unsubstituted aromatic Represents a heterocyclic group,
The sulfonamide derivative according to (1) or a pharmaceutically acceptable salt thereof, wherein R ⁴ represents substituted or unsubstituted C _6-14 aryl or a substituted or unsubstituted aromatic heterocyclic group.
(3) R ¹ and R ² are the same or different and are a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted C _1-10 alkyl, substituted or unsubstituted C _2-10 alkenyl, substituted or unsubstituted C _2-10 alkynyl, substituted or unsubstituted C _3-8 cycloalkyl, substituted or unsubstituted C _6-14 aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic ring The sulfonamide according to (2), which is a group, —COR ^5A (wherein R ^5A is as defined above) or —NR ^c R ^d (wherein R ^c and R ^d are as defined above), A derivative or a pharmacologically acceptable salt thereof.
(4) The sulfonamide derivative or the pharmaceutically acceptable salt thereof according to (1) or (2), wherein R ¹ and R ² are the same or different and are a hydrogen atom or halogen.
(5) The bicyclic heterocyclic group is a heterocyclic group selected from the group consisting of benzodioxolyl, benzodioxinyl, dihydrobenzofuranyl, benzotriazolyl, benzofuryl, indolyl and imidazolyl (1) The sulfonamide derivative in any one of-(4), or its pharmacologically acceptable salt.
(6) The sulfonamide derivative according to (1) or (2), wherein R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocyclic ring, or a pharmacological thereof Acceptable salt.
(7) The sulfonamide derivative or the pharmaceutically acceptable salt thereof according to (6), wherein the substituted or unsubstituted aromatic heterocycle formed together with adjacent carbon atoms is pyridine.
(8) The sulfonamide derivative according to (6) or (7) or a pharmacologically acceptable _salt thereof, wherein R ³ is a substituted or unsubstituted C _6-14 aryl or a substituted or unsubstituted aromatic heterocyclic group salt.
(9) The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to any one of (6) to (8), wherein R ⁴ is substituted or unsubstituted C _6-14 aryl.
(10) The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to any one of (6) to (8), wherein R ⁴ is 2,3-dichlorophenyl.
(11) The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to any one of (1) to (10), wherein Y is methylene or ethylene.
(12) The sulfonamide derivative or the pharmaceutically acceptable salt thereof according to any one of (1) to (10), wherein Y is methylene.
(13) A medicament comprising the sulfonamide derivative according to any one of (1) to (12) or a pharmacologically acceptable salt thereof as an active ingredient.
(14) A TARC and / or MDC function regulator comprising the sulfonamide derivative according to any one of (1) to (12) or a pharmacologically acceptable salt thereof as an active ingredient.
(15) Treatment and / or prevention of a disease involving TARC and / or MDC containing the sulfonamide derivative according to any one of (1) to (12) or a pharmacologically acceptable salt thereof as an active ingredient Agent.
(16) A therapeutic and / or prophylactic agent for a disease involving T cells, comprising as an active ingredient the sulfonamide derivative according to any one of (1) to (12) or a pharmacologically acceptable salt thereof.

  According to the present invention, it has a function-regulating action of TARC and / or MDC, and is a disease involving T cells such as various inflammatory diseases (for example, allergic diseases, autoimmune diseases, etc.), rejection at the time of transplantation, etc. Specifically, asthma, rhinitis, allergic rhinitis, chronic rhinitis, hay fever, conjunctivitis, allergic conjunctivitis, hives, psoriasis, atopic dermatitis, cutaneous pruritus, skin candidiasis, oral candidiasis, Rheumatoid arthritis, various collagen diseases, systemic lupus erythematosus, Sjogren's syndrome, cell rejection during organ transplantation, cancer, malignant lymphoma, leukemia such as adult T-cell leukemia (ATL), eosinophilic pneumonia, eosinophilic sinus Inflammation, eosinophilic rhinitis, interstitial cystitis, endometriosis, Churg-Strauss syndrome, sepsis, pain, neuralgia, insulin-dependent diabetes mellitus (IDDM) , Mycosis fungoides, contact dermatitis, cutaneous T-cell lymphoma, airway hypersensitivity, atherosclerosis, contact hypersensitivity, myocardial infarction, angina, arterial restenosis, ischemia reperfusion, stroke , Systemic anaphylaxis, drug allergy, insect bite, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis (UC), ileitis, enteritis, vaginitis, eczema, vasculitis, spondyloarthritis, scleroderma , Sulfoneamide derivatives useful for the treatment and / or prevention of multiple sclerosis, glomerulonephritis, osteoarthritis, chronic obstructive pulmonary disease (COPD), etc., suppression of cancer metastasis, etc. Acceptable salts can be provided.

Hereinafter, the compound represented by formula (I) is referred to as compound (I). The same applies to the compounds of other formula numbers.
In the definition of each group of general formula (I):
Examples of lower alkyl, lower alkyl portion of lower alkoxy, C _1-10 alkyl and C _1-10 alkyl portion of C _1-10 alkoxy include linear or branched alkyl having 1 to 10 carbon atoms, and more Specific examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl and the like.

Examples of lower alkenyl and C _2-10 alkenyl include linear or branched alkenyl having 2 to 10 carbon atoms, and more specifically vinyl, allyl, 1-propenyl, butenyl, pentenyl, hexenyl, heptenyl, Examples include octenyl, nonenyl, decenyl and the like.
Examples of lower alkynyl and C _2-10 alkynyl include linear or branched alkynyl having 2 to 10 carbon atoms, and more specifically, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, Examples include decynyl.

Examples of cycloalkyl and C _3-8 cycloalkyl include cycloalkyl having 3 to 8 carbon atoms, and more specifically, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.
Examples of the aryl moiety, aryl moiety of aryloxy, C _6-14 aryl and aryl moiety of C _6-14 aryloxy include aryl having 6 to 14 carbon atoms, and more specifically phenyl, naphthyl, anthranyl and the like. can give.

Examples of alkylene and C _1-10 alkylene include linear or branched alkylene having 1 to 10 carbon atoms, and more specifically, methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene. , Octamethylene, nonamethylene, decamethylene, propylene, ethylethylene, methylmethylene, dimethylmethylene and the like.

  As the aliphatic heterocyclic group, for example, a 5-membered or 6-membered monocyclic aliphatic heterocyclic group containing at least one atom selected from a nitrogen atom, an oxygen atom and a sulfur atom, and a 3- to 8-membered ring are condensed. A bicyclic or tricyclic fused-ring aliphatic heterocyclic group containing at least one atom selected from a nitrogen atom, an oxygen atom and a sulfur atom, and more specifically, aziridinyl, oxiranyl, azetidinyl, Tetrahydrofuranyl, thiolanyl, pyrrolidinyl, dioxolanyl, imidazolidinyl, pyrazolidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, piperidino, piperazinyl, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino, perhydroazepinyl, hydroazoperazinyl, hydroazoperazinyl per Tetrahydroquinori Le, tetrahydroisoquinolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, dihydro indolinium sulfonyl, such as dihydropyridyl and the like.

  As the aromatic heterocyclic group, for example, a 5- or 6-membered monocyclic aromatic heterocyclic group containing at least one atom selected from a nitrogen atom, an oxygen atom and a sulfur atom, and a 3- to 8-membered ring are condensed. A bicyclic or tricyclic fused ring aromatic heterocyclic group containing at least one atom selected from a nitrogen atom, an oxygen atom and a sulfur atom, and more specifically furyl, thienyl, pyrrolyl, Oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, benzoxazolyl, benzothienyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, purinyl, quinolyl, isoquinolyl, quinolyl, quinolyl , Phthalazinyl, cinnolinyl Quinoxalinyl, naphthyridinyl, pteridinyl, furazanyl, such as carbazolyl, and the like.

  Examples of the bicyclic heterocyclic group include a 5-membered or 6-membered monocyclic aliphatic heterocyclic group or monocyclic aromatic heterocyclic ring containing at least one atom selected from a nitrogen atom, an oxygen atom and a sulfur atom. A condensed bicyclic heterocyclic group containing at least one atom selected from a nitrogen atom, an oxygen atom and a sulfur atom, and a condensed aromatic heterocyclic group containing 3 to 8 membered rings fused to the group More specifically, benzoimidazolyl, benzotriazolyl, benzofuranyl, benzothienyl, purinyl, benzoxazolyl, benzothiazolyl, benzodioxolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, Quinazolinyl, benzodioxanyl, chromenyl, isochromanyl, chromanyl, dihydrobenzofura Le, and the like.

Halogen means each atom of fluorine, chlorine, bromine and iodine.
Examples of the aromatic heterocycle formed by R ¹ and R ² together with adjacent carbon atoms include furan, thiophene, pyrrole, imidazole, pyrazole, triazole, thiazole, thiadiazole, oxazole, isoxazole, Examples thereof include pyridine, pyrazine, pyrimidine, pyridazine, and triazine.

Substituted lower alkyl, substituted C _1-10 alkyl, substituted lower alkenyl, substituted C _2-10 alkenyl, substituted lower alkynyl, substituted C _2-10 alkynyl, substituted lower alkoxy, substituted C _1-10 alkoxy, substituted alkylene and substituted C _{1 As the} substituent in _-10 alkylene, it is the same or different, for example, the number of substitution 1-the number which can be substituted, Preferably it is 1-3.
Halogen, hydroxy, mercapto, azide, nitro, cyano, carboxy, carbamoyl, formyl, C _3-8 cycloalkyl optionally having 1 to 3 substituents selected from the following substituent group C, the following substitution C _6-14 aryl optionally having 1 to 3 substituents selected from group B, and 1 to 3 substituents selected from the following substituent group C An aliphatic heterocyclic group, an aromatic heterocyclic group optionally having 1 to 3 substituents selected from the following substituent group C;
C _1-10 alkoxy optionally having 1 to 3 substituents selected from the following substituent group A, having 1 to 3 substituents selected from the following substituent group A _Or C _2-10 alkenyloxy, C _3-8 cycloalkyloxy optionally having 1 to 3 substituents selected from the following substituent group C, 1 selected from substituent group B below C _6-14 aryloxy optionally having 3 substituents, aliphatic heterocyclic oxy optionally having 1 to 3 substituents selected from the following substituent group C, Aromatic heterocyclic oxy optionally having 1 to 3 substituents selected from Substituent Group C, 1 to 3 substituents selected from Substituent Group A below good C _2-11 alkanoyloxy, have 1 to 3 substituents selected from the following substituent group B Which may be C _7-15 aroyloxy, 1 selected 1-3 may have a substituent group C _1-10 alkylcarbamoyloxy selected from the following substituent group A, from the following substituent group A Di C _1-10 alkylcarbamoyloxy optionally having 3 substituents, C _6-14 aryl optionally having 1 to 3 substituents selected from the following substituent group B Rucarbamoyloxy,
C _1-10 alkylthio optionally having 1 to 3 substituents selected from the following substituent group A, having 1 to 3 substituents selected from the following substituent group B C _6-14 arylthio,
—NR ^x R ^y (wherein R ^x and R ^y are the same or different and each may have 1 to 3 substituents selected from a hydrogen atom and the following substituent group A _{1- 10} alkyl, C _2-10 alkenyl optionally having 1 to 3 substituents selected from the following substituent group A, 1 to 3 substituents selected from the following substituent group C Optionally selected from C _3-8 cycloalkyl, C _1-34 aryl optionally having 1 to 3 substituents selected from the following substituent group B, selected from the following substituent group C An aliphatic heterocyclic group optionally having 1 to 3 substituents, an aromatic heterocyclic group optionally having 1 to 3 substituents selected from the following substituent group C, It may have 1 to 3 substituents selected from substituent group a C _2-11 alkanoyl, the following substituent group B 1-3 may have a substituent group C _7-15 aroyl which is al selected, which may have 1 to 3 substituents selected from Substituent Group A C _{1- 10} alkoxycarbonyl, C _1-10 alkylsulfonyl optionally having 1 to 3 substituents selected from the following substituent group A, or 1 to 3 substituents selected from the following substituent group B Represents an _{optionally substituted} C _6-14 arylsulfonyl),
C _2-11 alkanoyl optionally having 1 to 3 substituents selected from the following substituent group A, having 1 to 3 substituents selected from the following substituent group C C _3-8 cycloalkylcarbonyl, C _7-15 aroyl optionally having 1 to 3 substituents selected from the following substituent group B, 1 to 1 selected from the following substituent group C An aliphatic heterocyclic carbonyl optionally having 3 substituents, an aromatic heterocyclic carbonyl optionally having 1 to 3 substituents selected from the following substituent group C, and the following substituents C _1-10 alkoxycarbonyl optionally having 1 to 3 substituents selected from group A, optionally having 1 to 3 substituents selected from the following substituent group B C _6-14 aryloxycarbonyl 1-3, selected from the following substituent group A Good C _1-10 optionally having substituent alkylcarbamoyl, 1-3 may have a substituent di C _1-10 alkylcarbamoyl selected from the following substituent group A, the following substituted C _6-14 arylcarbamoyl optionally having 1 to 3 substituents selected from Group B
C _1-10 alkylsulfonyl which may have 1 to 3 substituents selected from the following substituent group A, and 1 to 3 substituents selected from the following substituent group B C _6-14 arylsulfonyl which may be selected, C _1-10 alkylsulfamoyl optionally having 1 to 3 substituents selected from the following substituent group A, and selected from the following substituent group A Di-C _1-10 alkylsulfamoyl optionally having 1 to 3 substituents, and C ₆ optionally having 1 to 3 substituents selected from the following substituent group B _{And -14} arylsulfamoyl.

Examples of the substituent in the substituted aryl, the substituted C _6-14 aryl, the substituted aryloxy, and the substituted C _6-14 aryloxy include, for example, the following substituent groups A in addition to the groups exemplified in the above-mentioned substituted lower alkyl. C _1-10 alkyl optionally having 1 to 3 substituents selected, C _2-10 optionally having 1 to 3 substituents selected from the following substituent group A Examples include alkenyl.

A substituted cycloalkyl, a substituted C _3-8 cycloalkyl, a substituted aliphatic heterocyclic group, a substituted aromatic heterocyclic group, a bicyclic heterocyclic group, and R ¹ and R ² together with adjacent carbon atoms Examples of the substituent in the substituted aromatic heterocyclic ring to be formed include oxo and the like in addition to the groups exemplified in the substituents in the above substituted aryl.
Substituent group A is a good halogen, hydroxy, mercapto, azido, nitro, cyano, carboxy, carbamoyl, formyl, optionally having one to three substituents selected from substituent group F C _{3- 8} cycloalkyl, C _6-14 aryl optionally having 1 to 3 substituents selected from the following substituent group E, 1 to 3 substituents selected from the following substituent group F An aliphatic heterocyclic group which may have, an aromatic heterocyclic group which may have 1 to 3 substituents selected from the following substituent group F;
C _1-10 alkoxy optionally having 1 to 3 substituents selected from the following substituent group D, 1 to 3 substituents selected from the following substituent group E C _6-14 aryloxy,
C _1-10 alkylthio optionally having 1 to 3 substituents selected from the following substituent group D;
-NR ^xx R ^yy (wherein R ^xx and R ^yy are the same or different and each may have 1 to 3 substituents selected from a hydrogen atom and the following substituent group D _{1- 10} alkyl, C _3-8 cycloalkyl optionally having 1 to 3 substituents selected from the following substituent group F, 1 to 3 substituents selected from the following substituent group E C _6-14 aryl which may be present, C _2-11 alkanoyl which may have 1 to 3 substituents selected from the following substituent group D, and selected from the following substituent group E C _7-15 aroyl optionally having 1 to 3 substituents or C _1-10 alkoxycarbonyl optionally having 1 to 3 substituents selected from the following substituent group D To express),
C _2-11 alkanoyl optionally having 1 to 3 substituents selected from the following substituent group D, having 1 to 3 substituents selected from the following substituent group E C _1-15 aroyl, C _1-10 alkoxycarbonyl optionally having 1 to 3 substituents selected from the following substituent group D, 1 to 3 selected from the following substituent group E C _6-14 aryloxycarbonyl optionally having 1 substituent, C _1-10 alkylcarbamoyl optionally having 1 to 3 substituents selected from the following substituent group D, Di C _1-10 alkylcarbamoyl optionally having 1 to 3 substituents selected from Substituent Group D, having 1 to 3 substituents selected from Substituent Group E below Optionally C _6-14 arylcarbamoyl,
C _1-10 alkylsulfonyl which may have 1 to 3 substituents selected from the following substituent group D and 1 to 3 substituents selected from the following substituent group E It means a group consisting of C _6-14 arylsulfonyl which may be.

Substituent group D includes halogen, hydroxy, mercapto, amino, azide, nitro, cyano, carboxy, carbamoyl, formyl, C _6-14 aryl, aliphatic heterocyclic group, aromatic heterocyclic group,
C _1-10 alkoxy, C _6-14 aryloxy, hydroxy substituted C _1-10 alkoxy, C _1-10 alkoxy substituted C _1-10 alkoxy, amino substituted C _1-10 alkoxy, C _1-10 alkylamino substituted C _{1 -10} alkoxy, di-C _1-10 alkylamino substituted C _1-10 alkoxy, aliphatic heterocyclic oxy, aromatic heterocyclic oxy,
C _1-10 alkylthio,
C _1-10 alkylamino, diC _1-10 alkylamino, C _6-14 arylamino, diC _6-14 arylamino, C _1-10 alkoxycarbonylamino, hydroxy substituted C _1-10 alkylamino, C _{1- 10} alkoxy substituted C _1-10 alkylamino, amino substituted C _1-10 alkylamino, C _1-10 alkylamino substituted C _1-10 alkylamino, (di-C _1-10 alkylamino) substituted C _1-10 alkylamino,
C _2-11 alkanoyl, C _7-15 aroyl, C _1-10 alkoxycarbonyl, C _6-14 aryloxycarbonyl,
It means the group consisting of C _1-10 alkylsulfonyl and C _6-14 arylsulfonyl.

The substituent group E means a group obtained by adding C _1-10 alkyl and C _2-10 alkenyl to the substituent group D.
The substituent group F means a group obtained by adding oxo to the substituent group E.
Substituent group B is selected from C _1-10 alkyl which may have 1 to 3 substituents selected from substituent group D in substituent group A and substituent group D. The group which added the _C2-10 alkenyl which may have 1-3 substituents is meant.

Substituent group C means a group obtained by adding oxo to substituent group B.
C _1-10 alkyl, C _1-10 alkoxy, C _2-11 alkanoyloxy, C _1-10 alkylcarbamoyloxy, di-C _1-10 alkylcarbamoyloxy, C _1-10 alkylthio, C _2-11 shown here Alkanoyl, C _1-10 alkoxycarbonyl, C _1-10 alkylcarbamoyl, diC _1-10 alkylcarbamoyl, C _1-10 alkylsulfonyl, C _1-10 alkylsulfamoyl, diC _1-10 dialkylsulfamoyl, C _1-10 alkoxy substituted C _1-10 alkoxy, C _1-10 alkylamino substituted C _1-10 alkoxy, di-C _1-10 alkylamino substituted C _1-10 alkoxy, C _1-10 alkylamino, di-C _{1- 10} alkylamino, C _1-10 alkoxycarbonylamino, C Examples of the alkyl moiety of _1-10 alkoxy-substituted C _1-10 alkylamino, C _1-10 alkylamino-substituted C _1-10 alkylamino and (di-C _1-10 alkylamino) -substituted C _1-10 alkylamino include, for example, Examples are the groups given as examples of lower alkyl. Hydroxy substituted C _1-10 alkoxy, C _1-10 alkoxy substituted C _1-10 alkoxy, amino substituted C _1-10 alkoxy, C _1-10 alkylamino substituted C _1-10 alkoxy, di-C _1-10 alkylamino substituted C _1-10 alkoxy, hydroxy substituted C _1-10 alkylamino, C _1-10 alkoxy substituted C _1-10 alkylamino, amino substituted C _1-10 alkylamino, C _1-10 alkylamino substituted C _1-10 alkylamino and Examples of the alkylene moiety of (di-C _1-10 alkylamino) -substituted C _1-10 alkylamino include alkylenes in which one hydrogen atom has been removed from the groups exemplified in the lower alkyl.

An alkenyl moiety of C _2-10 alkenyl and C _2-10 alkenyloxy, a C _3-8 cycloalkyl, a C _3-8 cycloalkyloxy and a cycloalkyl moiety of C _3-8 cycloalkylcarbonyl, C _6-14 aryl, C _6-14 aryloxy, C _7-15 aroyloxy, C _6-14 arylcarbamoyloxy, C _6-14 arylcarbamoyl, C _6-14 arylsulfonyl, C _6-14 arylthio, C _7-15 aroyl, C _{6-14 aryloxycarbonyl, C 6-14} aryl _{sulfamoyl, C 6-14} aryl moiety of the arylamino and di _{C 6-14} arylamino, aliphatic heterocyclic group, aliphatic fatty heterocyclic oxy and aliphatic heterocyclic carbonyl Aromatic heterocyclic group moiety, aromatic heterocyclic group, aromatic heterocyclic group Examples of the aromatic heterocyclic group moiety and the halogen of cis and aromatic heterocyclic carbonyl include, for example, the above-mentioned lower alkenyl, cycloalkyl, aryl, aliphatic heterocyclic group, aromatic heterocyclic group and the groups exemplified in the halogen. Illustrated.

In addition, diC _1-10 alkylcarbamoyl, diC _1-10 alkylcarbamoyloxy, diC _1-10 alkylsulfamoyl, diC _1-10 alkylamino substituted C _1-10 alkoxy, diC ₁ shown here The two alkyl moieties of _-10 alkylamino and (diC _1-10 alkylamino) -substituted C _1-10 alkylamino may be the same or different, and the two aryl moieties of diC _6-14 arylamino may be the same May be different.

  The pharmacologically acceptable salt of compound (I) includes, for example, a pharmacologically acceptable acid addition salt, metal salt, ammonium salt, organic amine addition salt, amino acid addition salt and the like. Examples of the pharmacologically acceptable acid addition salt of compound (I) include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, phosphate, acetate, tartrate, gluconate, Examples include lactate, malate, oxalate, maleate, fumarate, citrate, benzoate, benzenesulfonate, methanesulfonate, and other organic acid salts. Examples of acceptable metal salts include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt and zinc salt, and pharmacologically acceptable. Examples of ammonium salts include ammonium and tetramethylammonium salts. Examples of pharmacologically acceptable organic amine addition salts include morpholine and piperidine. Salt. Examples of the pharmacologically acceptable amino acid addition salts such as lysine, glycine, phenylalanine, aspartic acid, addition salts, such as glutamic acid.

Next, the manufacturing method of compound (I) is demonstrated.
In the production method shown below, when the defined group changes under the conditions of the production method or is inappropriate for carrying out the method, a method for introducing and removing a protective group commonly used in organic synthetic chemistry [for example, Protective Groups in Organic Synthesis, 3rd Edition, by John Greene (TW Greene), John Wiley & Sons Incorporated (John Wiley Inc.) ) (1999)] and the like can be used to produce the target compound. Further, the order of reaction steps such as introduction of substituents can be changed as necessary.

Compound (I) can be produced according to the following steps.
Manufacturing method 1

(Wherein R ¹ , R ² , R ³ , R ⁴ and Y are as defined above, and X ¹ and X ² are the same or different and each represents a chlorine atom, bromine atom, iodine atom, methanesulfonyloxy group) , Represents a leaving group such as p-toluenesulfonyloxy group and trifluoromethanesulfonyloxy group)
Process 1
Compound (IV) is compound (II) in a suitable solvent in an amount of 1 to 100 equivalents, preferably 1 to 2 equivalents of compound (III), and optionally 1 to 100 equivalents, preferably 3 to 4 equivalents. In the presence of a suitable base at a temperature between −10 ° C. and the boiling point of the solvent used, preferably at a temperature between 0 ° C. and room temperature, for 5 minutes to 72 hours.

  Suitable solvents include, for example, tetrahydrofuran (THF), dioxane, 1,2-dimethoxyethane, benzene, toluene, xylene, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMA), N-methyl. Examples include pyrrolidone (NMP), pyridine, chloroform, dichloromethane, ethyl acetate, acetonitrile, and the like. These can be used alone or in combination, and among them, THF is preferable.

  Suitable bases include, for example, alkali metal hydrides such as sodium hydride and potassium hydride, metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide, Alkali metal salts such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] unde-7-cene (DBU), 1,5-diazabicyclo [4.3.0] none Organic bases such as -5-ene (DBN) and N, N-dimethylaminopyridine (DMAP), Amberlyst A-21 (Rohm and Haas), AG1-X8 (BioRad), polyvinylpyridine, morpholino Solid bases such as methylpolystyrene Gerare, among them sodium hydride is preferred.

Compound (II) can be obtained, for example, as a commercial product, or can be obtained by a known method (for example, the method described in US3898216) or according to the method described in Reference Example 1 or 2.
Compound (III) can be obtained, for example, as a commercial product.
Process 2
Compound (I) is obtained by converting 1 to 20 equivalents of Compound (IV) in the presence of 1 to 100 equivalents, preferably 1 to 10 equivalents of a suitable base, without solvent or in a solvent inert to the reaction. , Preferably by reacting with 1 to 2 equivalents of compound (V) at a temperature between 0 ° C. and 200 ° C., preferably at a temperature between room temperature and 40 ° C., for 5 minutes to 72 hours. it can.

Examples of the solvent inert to the reaction include THF, dioxane, 1,2-dimethoxyethane, benzene, toluene, xylene, DMF, DMA, NMP, pyridine, chloroform, dichloromethane, ethyl acetate, acetonitrile, and the like. They can be used alone or in combination, and among them, THF or DMF is preferable.
Suitable bases include, for example, alkali metal hydrides such as sodium hydride and potassium hydride, metal alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide, n-butyllithium, sec-butyllithium, tert- Organic metal bases such as butyl lithium, metal amides such as lithium diisopropylamide (LDA) and lithium hexamethyldisilazane (LiHMDS), alkali metal salts such as sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate , Pyridine, triethylamine, diisopropylethylamine, organic bases such as DBU, DBN, DMAP, N-methylmorpholine, Amberlyst A-21 (Rohm and Haas), AG1-X8 (Biorace) Solid base such as polyvinyl pyridine, morpholinomethyl polystyrene, and the like. Among them, sodium hydride or potassium tert-butoxide is preferable.

Compound (V) can be obtained, for example, as a commercial product.
Manufacturing method 2

(Wherein R ¹ , R ² , R ³ , R ⁴ , Y, X ¹ and X ² are the same as defined above)
Process 1
Compound (IV) is compound 1 to 10 equivalents, preferably 1 to 100 equivalents, preferably 1 to 100 equivalents of compound (VI) in the absence of solvent or in a solvent inert to the reaction. It can be prepared by reacting in the presence of 5 equivalents of a suitable base at a temperature between −10 ° C. and 150 ° C., preferably at a temperature between 30 ° C. and 80 ° C. for 5 minutes to 72 hours.

Examples of the solvent inert to the reaction include THF, dioxane, 1,2-dimethoxyethane, benzene, toluene, xylene, DMF, DMA, NMP, pyridine, chloroform, dichloromethane, ethyl acetate, acetonitrile, and the like. They can be used alone or in combination, and among them, THF or DMF is preferable.
Suitable bases include, for example, alkali metal hydrides such as sodium hydride and potassium hydride, metal alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide, n-butyllithium, sec-butyllithium, tert- Organometallic bases such as butyl lithium, metal amides such as LDA and LiHMDS, alkali metal salts such as sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, pyridine, triethylamine, diisopropylethylamine, DBU, DBN, Solid bases such as DMAP, organic bases such as N-methylmorpholine, Amberlyst A-21 (Rohm and Haas), AG1-X8 (BioRad), polyvinylpyridine, morpholinomethylpolystyrene, etc. Body bases and the like. Among them, sodium hydride or potassium carbonate is preferable.

Compound (VI) can be obtained, for example, as a commercial product or according to a known method (for example, the method described in WO2003 / 059893).
Compound (VII) can be obtained, for example, as a commercial product.
Process 2
Compound (I) can be produced by performing the same operation as in step 2 of production method 1, using compound (IV) obtained in step 1 above.
Production method 3

(Wherein R ¹ , R ² , R ³ , R ⁴ , Y, X ¹ and X ² are the same as defined above)
Process 1
Compound (VIII) can be produced by using compound (II) and performing the same operation as in step 2 of production method 1.
Process 2
Compound (I) can be produced by performing the same operation as in Step 1 of Production Method 1 using Compound (VIII) obtained in Step 1 above.

Conversion of the functional group contained in R ¹ , R ² , R ³ , R ⁴ or Y in the compound (I) can be carried out by a known method [for example, Comprehensive Organic Transformations, R.C. C. The method described in Larock (1989) etc.] or in accordance therewith.

Moreover, the compound (I) which has a desired functional group in a desired position can be obtained by implementing combining said method suitably.
The intermediates and target compounds in each of the above production methods are isolated and purified by separation and purification methods commonly used in synthetic organic chemistry, such as filtration, extraction, washing, drying, concentration, recrystallization, and various chromatography. be able to. The intermediate can be subjected to the next reaction without any particular purification.

Some compounds (I) may have stereoisomers such as positional isomers, geometric isomers, optical isomers, tautomers, etc., but the present invention includes all such possibilities. Isomers and mixtures thereof.
When it is desired to obtain a salt of compound (I), it can be purified as it is when compound (I) is obtained in the form of a salt. When it is obtained in a free form, compound (I) can be obtained in an appropriate solvent. It may be isolated or purified by dissolving or suspending and forming a salt by adding an acid or a base.

Compound (I) and pharmacologically acceptable salts thereof may exist in the form of adducts with water or various solvents, and these adducts are also included in the sulfonamide derivatives of the present invention. The
Specific examples of the compound (I) obtained by the present invention are shown in Tables 1 and 2. However, the compound of the present invention is not limited to these.

Next, the pharmacological action of compound (I) will be specifically described with reference to test examples.
Test Example 1: Inhibitory effect on binding of [ ¹²⁵ I] -TARC to Hut78 cells 20 mmol / L 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid (HEPES; Nacalai Tesque) and 0.1 wt / l RPMI-1640 medium (Sigma Aldrich Japan) containing volume% bovine serum albumin (Seikagaku Corporation) was adjusted to pH = 7.0 with sodium bicarbonate (Wako Pure Chemical Industries) (binding / wash buffer solution). In a 96-well round bottom plate (Corning Coaster), (a) 60 μL (3 × 10 ⁵ cells) of Hut78 cells (ATCC No. TIB-161) suspended in the obtained binding / wash buffer solution (3 × 10 ⁵ cells), (b) 10 mmol 20 μL of a test compound solution diluted with a binding / wash buffer solution to each concentration of a dimethyl sulfoxide solution containing / L of the test compound and 810 Bq [ ¹²⁵ I] -TARC (Amersham Biosciences) diluted with a binding / wash buffer solution ) 20 μL was added to make a total volume of 100 μL and reacted at room temperature for 2 hours.

The reaction product in each well containing the above Hut-78 cells was added to each well of a glass filter plate (Unifilter GF / B96, Packard Bioscience) and rapidly used with Filtermate 196 (Packard Bioscience). Filtered. The glass filter plate was used after adding 50 μL of a polyethyleneimine solution (Nacalai Tesque) diluted to 0.3 wt / vol% with a binding / wash buffer solution to each well. The glass filter in each well was washed with a binding / wash buffer solution at 4 ° C., 50 μL of microcinch 20 (Packard Bioscience) was added, and the amount of radioactivity on the glass filter was measured using Topcount NXT ^™ (Packard Bioscience). It was measured.

  The binding inhibition rate (%) of the test compound was calculated according to the following formula.

The total amount of binding is the amount of [ ¹²⁵ I] -TARC binding radioactivity in the absence of the test compound.
The amount of binding when the test compound is added is the amount of [ ¹²⁵ I] -TARC binding radioactivity in the presence of the test compound.
The non-specific binding amount is the amount of [ ¹²⁵ I] -TARC binding radioactivity when a binding experiment is performed with a sufficient amount of unlabeled TARC added.

  The results are shown in Table 3.

Compounds 3, 8 and 12 showed excellent inhibitory action on TARC binding to Hut78 cells. That is, it is considered that compound (I) can regulate the function of TARC.
On the other hand, cells migrated with TARC or MDC are known to have high IL-4 production ability and low IFN-γ production ability [International Immunology, Volume 11, p. 81 (1999)]. In other words, cells migrated by TARC and MDC play an important role in allergic reaction, and CCR4 and its ligands TARC and MDC are thought to be deeply related to the pathology of allergy [Molecular Immunology]. 38, p. 881 (2002); Allergy, 57, p. 180 (2002)].

For example, there are the following reports.
(I) Increased CCR4-positive T cells in peripheral blood [American Journal of Respiratory and Critical Care Medicine, 164 , P. 745 (2001)], increased TARC in peripheral blood and sputum [Allergy, 57, p. 173 (2002)], CCR4-positive T cell infiltration by antigen stimulation in lung tissue [Journal of Clinical Investigation, 107, p. 1357 (2001)]. In mice administered with an antibody against TARC, the pathology of asthma was strongly suppressed [Journal of Immunology, 166, p. 2055 (2001)], and anti-MDC antibodies have also been shown to suppress asthma pathology in a mouse asthma model [Journal of Immunology, 163, p. 403 (1999)].
(Ii) Increased TARC in peripheral blood and alveolar lavage fluid in patients with eosinophilic pneumonia [American Journal of Respiratory and Critical Care Medicine (American Journal of (Respiratory and Critical Care Medicine), 165, p. 1125 (2002)].
(Iii) In patients with rhinitis, TARC concentration increases in peripheral blood [Allergy, 57, p. 180 (2002)], it is known that TARC, a CCR4 ligand, is produced from human nasal mucosa [Clinical and Experimental Allergy, Vol. 31, p. 1923 (2001)].
(Iv) It has been reported that when corneal fibroblasts are stimulated with Th2 cytokines such as IL-4 and TNF-α, TARC production is increased, and CCR4-positive cells are assumed to be involved in allergic conjunctivitis. [Biochemical and Biophysical Research Communications, 279, p. 1 (2000)].
(V) In patients with atopic dermatitis, an increase in TARC concentration according to severity in peripheral blood [Journal of Allergy Clinical Immunology, vol. 107, p. 535 (2001)], and an increase in the concentration of MDC in peripheral blood according to the severity [Clinical and Experimental Immunology, 127, p. 270 (2002)]. Further, in patients with atopic dermatitis, an increase in the proportion of CCR4 positive cells contained in CD4 positive T cells in peripheral blood has been reported [Journal of Investigative Dermatology (Journal of Investigative Dermatology). Dermatology), 117, p. 188 (2001)].
(Vi) In psoriasis, it has been reported that the infiltration of CCR4-positive cells increases around the blood vessels in the skin of the lesion [Laboratory Investigation, Vol. 81, p. 335 (2001)].
(Vii) In patients whose oral skin was infected with Candida albicans , it was reported that increases in CCR4-positive T cells and MDC-producing dendritic cells were observed in the epidermis and dermis at the site of inflammation caused by infection. [American Journal of Pathology, 158, p. 1263 (2000)].
(Viii) Infiltration of CCR4-positive cells into synovial tissue in rheumatoid arthritis [Arthritis and Rheumatism, vol. 44, p. 2750 (2001)], and increase in CCR4-positive cells in peripheral blood during periods of high systemic lupus erythematosus disease activity [Journal of Leukocyte Biology, vol. 70, p. . 749 (2001)].
(Ix) Sepsis is less likely to occur in CCR4 knockout mice [Journal of Experimental Medicine, Vol. 191, p. 1755 (2000)].
(X) It is known that cells expressing CCR4 also exist in leukemia [Blood, Vol. 96, p. 685 (2000)], especially in adult T-cell leukemia (ATL), CCR4 expression is significantly observed [Blood, Vol. 99, p. 1505 (2002)].
(Xi) TARC has been reported to be involved in pathology in Mycosis fungoides [Journal of American Academy of Dermatology, Vol. 48, p. . 23 (2003)].
(Vii) CCR4 is expressed in nerve cells, particularly substance P neurons in dorsal root ganglia, and stimulation of nerve cells by MDC increases intracellular calcium and releases substance P, a pain-causing substance [Journal Journal of Neuroscience, Volume 21, p. 5027 (2001)].
(Xiii) It has been reported that an anti-mouse MDC antibody suppresses the onset of diabetes in insulin-dependent diabetes model mice (NOD mice) [Journal of Clinical Investigation, Vol. 110. , P. 1675 (2002)].

  Therefore, the function of TARC and / or MDC is regulated [TARC and / or MDC binding to T cells, or TARC and / or MDC binding to CCR4 (CCR4 antagonism) The compound (I) of the present application or a pharmaceutically acceptable salt thereof is expected as a therapeutic agent for allergic diseases, for example. In particular, it is considered effective for the treatment of asthma, rhinitis, allergic conjunctivitis, atopic dermatitis and the like. Furthermore, the compound (I) of the present application or a pharmacologically acceptable salt thereof is also expected as a therapeutic agent for malignant lymphoma, leukemia and the like, particularly for treatment of adult T cell leukemia (ATL) and cutaneous T cell lymphoma. It is considered effective.

  Compound (I) or a pharmacologically acceptable salt thereof is, for example, eosinophilic pneumonia, eosinophilic sinusitis, eosinophilic polyrhinitis, endometriosis, Churg-Stras Syndrome (Churg-Strauss Syndrome), Psoriasis, Rheumatoid Arthritis, Systemic Lupus Erythematosus, Sepsis, Interstitial Cystitis, Insulin Dependent Diabetes Mellitus (IDDM), Oral Candidiasis, Mycosis fungiides, Contact Skin It is thought to be effective in treating flames and urticaria.

Furthermore, compound (I) or a pharmacologically acceptable salt thereof is expected to have an inhibitory effect on pain, neuralgia, etc. due to inhibition of release of a pain-causing substance. Acceptable salts are considered effective in the treatment of cutaneous pruritus and the like.
Compound (I) or a pharmacologically acceptable salt thereof can be administered alone as it is, but it is usually desirable to provide it as various pharmaceutical preparations. These pharmaceutical preparations are used for animals or humans.

  The pharmaceutical preparation according to the present invention may contain Compound (I) or a pharmacologically acceptable salt thereof as an active ingredient alone or as a mixture with any other active ingredient for treatment. These pharmaceutical preparations are produced by any method well known in the technical field of pharmaceutics by mixing the active ingredient together with one or more pharmaceutically acceptable carriers.

As the administration route, it is desirable to use one that is most effective in the treatment, and examples thereof include oral administration and parenteral administration such as intravenous administration.
Examples of the dosage form include tablets and injections.
For example, tablets suitable for oral administration can be produced using excipients such as lactose, disintegrants such as starch, lubricants such as magnesium stearate, binders such as hydroxypropylcellulose, and the like.

For example, an injection suitable for parenteral administration can be produced using a salt solution, a glucose solution or a mixed solution of a saline solution and a glucose solution.
The dose and frequency of administration of Compound (I) or a pharmacologically acceptable salt thereof vary depending on the administration form, patient age, body weight, nature or severity of symptoms to be treated, etc. In the range of 0.01 to 1000 mg, preferably 0.05 to 500 mg per adult, it is administered once to several times a day. In the case of parenteral administration such as intravenous administration, 0.001 to 1000 mg, preferably 0.01 to 300 mg, is usually administered once or several times a day for each adult. However, the dose and the number of doses vary depending on the various conditions described above.

  EXAMPLES Hereinafter, although an Example and a reference example demonstrate this invention further more concretely, the scope of the present invention is not limited to these Examples. The compound numbers in the following examples correspond to the compound numbers shown as specific examples in Table 1.

N- [3- (Benzo [1,3] dioxol-5-ylmethoxy) -5-chloropyrazin-2-yl] -2,3-dichlorobenzenesulfonamide (Compound 1)
2,3-Dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide (70 mg) obtained in Reference Example 1 was dissolved in DMF (2 mL), and potassium tert-butoxide (50 mg) was added, and the mixture was stirred at room temperature for 1 minute. Piperonyl alcohol (34 mg) was added, and the mixture was further stirred for 4 hours. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography, and then recrystallized from hexane-ethyl acetate to obtain Compound 1 (21 mg).
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 5.28 (s, 2H), 6.04 (s, 2H), 6.92 (d, J = 8.1 Hz, 1H), 6.99 (dd, J = 8.1, 1.5 Hz, 1H), 7.12 (d, J = 1.5 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.80 (s, 1H), 7.91 (dd, J = 8.1, 1.5 Hz, 1H) , 8.04 (dd, J = 8.1, 1.5 Hz, 1H).

2,3-dichloro-N- [5-chloro-3- (2,3-dihydrobenzo [1,4] dioxan-6-ylmethoxy) pyrazin-2-yl] benzenesulfonamide (compound 2)
Using 2,3-dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide (70 mg) and 3,4-ethylenedioxybenzyl alcohol (37 mg) obtained in Reference Example 1 Then, compound 2 (41 mg) was obtained in the same manner as in Example 1.
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 4.25 (s, 4H), 5.25 (s, 2H), 6.85 (d, J = 8.1 Hz, 1H), 6.95 (dd, J = 8.1, 1.8 Hz, 1H), 7.05 (d, J = 1.8 Hz, 1H), 7.54 (t, J = 8.1 Hz, 1H), 7.80 (s, 1H), 7.91 (dd, J = 8.1, 1.8 Hz, 1H) , 8.04 (dd, J = 8.1, 1.8 Hz, 1H).

2,3-dichloro-N- [5-chloro-3- (2,3-dihydrobenzofuran-5-ylmethoxy) pyrazin-2-yl] benzenesulfonamide (compound 3)
2,3-Dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide (70 mg) and 2,3-dihydrobenzofuran-5-ylmethanol (34 mg) obtained in Reference Example 1 Was used in the same manner as in Example 1 to obtain compound 3 (38 mg).
¹ H-NMR (270 MHz, DMSO-d ₆ , δ): 3.19 (t, J = 8.8 Hz, 2H), 4.54 (t, J = 8.8 Hz, 2H), 5.28 (s, 2H), 6.76 (d , J = 8.1 Hz, 1H), 7.22 (dd, J = 8.1, 1.4 Hz, 1H), 7.35 (s, 1H), 7.53 (t, J = 8.1 Hz, 1H), 7.79 (s, 1H), 7.90 (d, J = 8.1 Hz, 1H), 8.03 (dd, J = 8.1, 1.4 Hz, 1H).

2,3-Dichloro-N- [5-chloro-3- (1-methyl-1H-1,2,3-benzotriazol-5-ylmethoxy) pyrazin-2-yl] benzenesulfonamide (Compound 4)
2,3-Dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide (70 mg) obtained in Reference Example 1 and 1-methyl-1H-1,2,3-benzotriazole- Compound 4 (31 mg) was obtained in the same manner as in Example 1 using 5-yl) methanol (37 mg).
¹ H-NMR (270 MHz, DMSO-d ₆ , δ): 4.33 (s, 3H), 5.56 (s, 2H), 7.53 (t, J = 8.1 Hz, 1H), 7.69 (dd, J = 8.6, 1.4 Hz, 1H), 7.84-7.89 (m, 3H), 8.06 (dd, J = 7.8, 1.4 Hz, 1H), 8.28 (s, 1H).

N- [3- (Benzofuran-2-ylmethoxy) -5-chloropyrazin-2-yl] -2,3-dichlorobenzenesulfonamide (Compound 5)
Using 2,3-dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide (70 mg) and benzofuran-2-ylmethanol (33 mg) obtained in Reference Example 1 Compound 5 (41 mg) was obtained in the same manner as in Example 1.
¹ H-NMR (270 MHz, DMSO-d ₆ , δ): 5.30 (s, 2H), 7.11 (s, 1H), 7.28 (dd, J = 7.6, 1.1 Hz, 1H), 7.37 (dd, J = 7.6, 1.4 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.69 (d, J = 7.6 Hz, 1H), 7.84-7.88 (m, 2H), 8.04 (dd, J = 8.0, 1.4 Hz, 1H).

2,3-Dichloro-N- [5-chloro-3- (1-methylindol-2-ylmethoxy) pyrazin-2-yl] benzenesulfonamide (Compound 6)
Using 2,3-dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide (70 mg) and 1-methylindol-2-ylmethanol (36 mg) obtained in Reference Example 1 Then, Compound 6 (48 mg) was obtained in the same manner as in Example 1.
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 3.80 (s, 3H), 5.53 (s, 2H), 6.65 (s, 1H), 7.05 (t, J = 6.9 Hz, 1H), 7.20 (t, J = 7.2 Hz, 1H), 7.42-7.52 (m, 2H), 7.56 (d, J = 8.1 Hz, 1H), 7.77 (br s, 2H), 8.02 (d, J = 6.9 Hz, 1H ).

2,3-Dichloro-N- [5-chloro-3- (benzimidazol-2-ylmethoxy) pyrazin-2-yl] benzenesulfonamide (Compound 7)
Using 2,3-dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide (70 mg) and benzimidazol-2-ylmethanol (36 mg) obtained in Reference Example 1, Compound 7 (48 mg) was obtained in the same manner as in Example 1.
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 5.40 (s, 2H), 7.16-7.21 (m, 2H), 7.31 (s, 1H), 7.35 (d, J = 7.8 Hz, 1H) , 7.50 (d, J = 7.8 Hz, 1H), 7.59-7.64 (m, 2H), 7.91-7.95 (m, 2H).

2,3-dichloro-N- [5-chloro-3- (5-methoxycarbonylbenzimidazol-2-ylmethoxy) pyrazin-2-yl] benzenesulfonamide (Compound 8)
2,3-Dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide (70 mg) and methyl 2-hydroxymethylbenzimidazole-5-carboxylate (46 mg) obtained in Reference Example 1 ) Was used to obtain Compound 8 (48 mg) in the same manner as in Example 1.
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 3.88 (s, 3H), 5.65 (s, 2H), 7.36 (t, J = 8.1 Hz, 1H), 7.72 (d, J = 8.4 Hz , 1H), 7.87-7.95 (m, 4H), 8.11 (dd, J = 8.1, 1.5 Hz, 1H), 8.23 (s, 1H).

N- [3- (5-Carboxybenzimidazol-2-ylmethoxy) -5-chloropyrazin-2-yl] -2,3-dichlorobenzenesulfonamide (Compound 9)
2,3-Dichloro-N- [5-chloro-3- (5-methoxycarbonylbenzimidazol-2-ylmethoxy) pyrazin-2-yl] benzenesulfonamide (160 mg) obtained in Example 8 was added to methanol (20 After adding potassium hydroxide aqueous solution (6 mol / L, 10 mL) and stirring at room temperature for 1 hour, THF (5 mL) was added and stirred for 1 hour. After evaporating the solvent under reduced pressure, water was added, neutralized with hydrochloric acid (2 mol / L), and the precipitated crystals were collected by filtration to obtain Compound 9 (70 mg).
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 5.42 (s, 2H), 7.33-7.38 (m, 2H), 7.49 (d, J = 7.5 Hz, 1H), 7.62 (dd, J = 8.1, 1.5 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H), 7.95 (dd, J = 8.1, 1.2 Hz, 1H), 8.11 (br s, 1H).

2,3-dichloro-N- [5-chloro-3- (5-dimethylcarbamoylbenzimidazol-2-ylmethoxy) pyrazin-2-yl] benzenesulfonamide (Compound 10)
N- [3- (5-Carboxybenzimidazol-2-ylmethoxy) -5-chloropyrazin-2-yl] -2,3-dichlorobenzenesulfonamide (30 mg) obtained in Example 9 and dimethylamine hydrochloride Salt (23 mg), hydroxybenzotriazole (43 mg) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (54 mg) were dissolved in DMF (3 mL) and diisopropylethylamine (49 μL) And stirred at room temperature for 12 hours. To the reaction mixture was added saturated brine, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography and then recrystallized from hexane-ethyl acetate to obtain Compound 10 (21 mg).
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 2.98 (s, 6H), 5.51 (s, 2H), 7.26 (dd, J = 8.1, 1.5 Hz, 1H), 7.39-7.46 (m, 2H), 7.52-7.74 (m, 3H), 7.95-8.02 (m, 2H).

2,3-dichloro-N- [2- (pyridin-3-ylmethoxy) pyrido [2,3-b] pyrazin-3-yl] benzenesulfonamide (Compound 11)
Pyridine-3-methanol (30 μL) was dissolved in THF (2 mL), sodium hydride (60% in oil, 20 mg) was added, and the mixture was stirred at room temperature for 15 min. 2,3-Dichloro-N- (2-chloropyrido [2,3-b] pyrazin-3-yl) benzenesulfonamide (0.10 g) obtained in Reference Example 2 was added to the obtained mixture, and 2 at room temperature was added. Stir for hours. The mixture was neutralized with 5% aqueous citric acid solution, ethyl acetate (20 mL) and water (20 mL) were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine (30 mL). The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure to obtain a light brown solid. The obtained solid was washed with ethyl acetate (20 mL), and then dried under reduced pressure to obtain Compound 11 (0.07 g).
¹ H-NMR (270 MHz, DMSO-d ₆ , δ): 5.56 (s, 2H), 7.41-7.46 (m, 2H), 7.48 (t, J = 7.9 Hz, 1H), 7.77 (dd, J = 8.1, 1.7 Hz, 1H), 7.94 (dt, J = 7.8, 1.7 Hz, 1H), 8.18 (dd, J = 8.1, 1.7 Hz, 1H), 8.33-8.39 (m, 2H), 8.55 (dd, J = 4.8, 1.3 Hz, 1H), 8.75 (d, J = 2.1 Hz, 1H).

2,3-Dichloro-N- [2- (1-methyl-1H-benzotriazol-5-ylmethoxy) pyrido [2,3-b] pyrazin-3-yl] benzenesulfonamide (Compound 2-2)
2,3-Dichloro-N- (2-chloropyrido [2,3-b] pyrazin-3-yl) benzenesulfonamide (0.16 g) obtained in Reference Example 2 and (1-methyl-1H-benzotriazole- Compound 12 (0.12 g) was obtained in the same manner as in Example 11 using 5-yl) methanol (80 mg).
¹ H-NMR (270 MHz, DMSO-d ₆ , δ): 4.31 (s, 3H), 5.69 (s, 2H), 7.41-7.51 (m, 2H), 7.70-7.78 (m, 2H), 7.89 ( d, J = 8.3 Hz, 1H), 8.19-8.21 (m, 2H), 8.30 (d, J = 7.9 Hz, 1H), 8.38 (d, J = 5.8 Hz, 1H).

N- (2-Benzyloxypyrido [2,3-b] pyrazin-3-yl) -2,3-dichlorobenzenesulfonamide (Compound 13)
Using 2,3-dichloro-N- (2-chloropyrido [2,3-b] pyrazin-3-yl) benzenesulfonamide (0.10 g) and benzyl alcohol (50 μL) obtained in Reference Example 2, Compound 13 (0.12 g) was obtained in the same manner as in Example 11.
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 5.53 (s, 2H), 7.34-7.53 (m, 7H), 7.78 (dd, J = 8.1, 1.5 Hz, 1H), 8.19 (dd, J = 7.9, 1.5 Hz, 1H), 8.33-8.38 (m, 2H).

2,3-Dichloro-N- [2- (4-methoxybenzyloxy) pyrido [2,3-b] pyrazin-3-yl] benzenesulfonamide (Compound 14)
2,3-Dichloro-N- (2-chloropyrido [2,3-b] pyrazin-3-yl) benzenesulfonamide (0.10 g) and 4-methoxybenzyl alcohol (60 μL) obtained in Reference Example 2 were used. Was used to give compound 14 (0.11 g) in the same manner as in Example 11.
¹ H-NMR (270 MHz, DMSO-d ₆ , δ): 3.76 (s, 3H), 5.45 (s, 2H), 6.95 (d, J = 8.8 Hz, 2H), 7.45-7.51 (m, 4H) , 7.78 (d, J = 7.2 Hz, 1H), 8.19 (dd, J = 7.9, 1.7 Hz, 1H), 8.35-8.37 (m, 2H).
Reference example 1
2,3-Dichloro-N- (3,5-dichloropyrazin-2-yl) benzenesulfonamide
2-Amino-3,5-dichloropyrazine (2.0 g) was dissolved in THF (200 mL), and sodium hydride (60% in oil, 731 mg) was added at 0 ° C. After stirring for 10 minutes, 2,3-dichlorobenzenesulfonyl chloride (3.29 g) was added, and the mixture was stirred at the same temperature for 20 minutes and further at room temperature for 2 hours. The solvent was removed under reduced pressure, saturated brine was added, and the mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off, ethyl acetate was added to the residue, and the precipitated crystals were separated by filtration. Hydrochloric acid (1 mol / L) was added to the filtrate, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was mixed with the crystals separated by filtration, and recrystallized from hexane-ethyl acetate to obtain the title compound (3.2 g).
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 7.47 (d, J = 8.1 Hz, 1H), 7.80 (dd, J = 8.1, 1.5 Hz, 1H), 7.99-8.02 (m, 2H) .
Reference example 2
2,3-Dichloro-N- (2-chloropyrido [2,3-b] pyrazin-3-yl) benzenesulfonamide 2,3-dichloropyrido [2,3-b] pyrazine described in US Pat. No. 3,898,216 (0.50 g ) Was dissolved in DMF (10 mL), 2,3-dichlorobenzenesulfonamide (0.57 g, 2.5 mmol) and potassium carbonate (1.45 g) were added, and the mixture was stirred at 70 ° C. for 3 hours. After cooling to room temperature, the reaction mixture was filtered, and the solvent was distilled off from the filtrate under reduced pressure to obtain a brown oil. Water (10 mL) was added to the oil, the pH of the solution was adjusted to 4 with 5% aqueous citric acid solution, and the precipitated solid was collected by filtration. The obtained solid was washed with ethyl acetate (20 mL) and dried under reduced pressure to give the title compound (0.68 g).
¹ H-NMR (300 MHz, DMSO-d ₆ , δ): 7.51 (t, J = 8.3 Hz, 1H), 7.56 (dd, J = 8.3, 5.9 Hz, 1H), 7.80 (dd, J = 7.9, 1.3 Hz, 1H), 8.21 (dd, J = 7.9, 1.7 Hz, 1H), 8.59-8.62 (m, 2H).
Formulation Example 1
Tablet (Compound 3)
A tablet having the following composition is prepared by a conventional method. Compound 3, 40 g, lactose 286.8 g and potato starch 60 g are mixed, and 10% aqueous solution of hydroxypropylcellulose 120 g is added thereto. The obtained mixture is kneaded by a conventional method, granulated and dried, and then sized to obtain granules for tableting. To this was added 1.2 g of magnesium stearate, mixed, and tableted with a tableting machine (RT-15 model, manufactured by Kikusui Co., Ltd.) having a 8 mm diameter punch to contain tablets (containing 20 mg of active ingredient per tablet). To get).
Formulation Compound 3 20 mg
Lactose 143.4 mg
Potato starch 30 mg
Hydroxypropylcellulose 6 mg
Magnesium stearate 0.6 mg
200 mg
Formulation Example 2
Injection (Compound 12)
An injection having the following composition is prepared by a conventional method. Compound 12, 1 g and D-mannitol 5 g were added to and mixed with distilled water for injection. Further, hydrochloric acid and sodium hydroxide aqueous solution were added to adjust the pH to 6, and then the total amount was 1000 with distilled water for injection.
Set to mL. The obtained mixed solution is aseptically filled into glass vials by 2 mL to obtain an injection (containing 2 mg of active ingredient per vial).
Formulation Compound 12 2 mg
D-mannitol 10 mg
Hydrochloric acid appropriate amount Sodium hydroxide aqueous solution appropriate amount
Distilled water for injection
2.00 mL

Claims (16)

Formula (I)

<In the formula, R ¹ and R ² are the same or different and each represents a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted Or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted lower alkoxy, -NR ^a R ^b ( In the formula, R ^a and R ^b are the same or different and each is a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted cycloalkyl, substituted Or unsubstituted aryl, substituted or unsubstituted aliphatic heterocyclic group or substituted or unsubstituted Aromatic a heterocyclic group) or -COR ⁵ [wherein, ^{R 5} is hydroxy, substituted or unsubstituted lower alkoxy, substituted or unsubstituted ^aryloxy, in ^-NR aa ^{R bb (wherein, R aa} and R ^bb represents the same as R ^a and R ^b , respectively, and represents an aliphatic heterocyclic group or an aromatic heterocyclic group], or R ¹ and R ² together with adjacent carbon atoms. To form a substituted or unsubstituted aromatic heterocycle,
(I) R ¹ and R ² are the same or different and are a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl, substituted or Unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted lower alkoxy, —NR ^a R ^b (formula Wherein R ^a and R ^b are as defined above) or —COR ⁵ (wherein R ⁵ is as defined above),
Y represents alkylene, R ³ represents a substituted or unsubstituted bicyclic heterocyclic group,
R ⁴ represents 2,3-dichlorophenyl,
(Ii) when R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocycle,
Y represents a substituted or unsubstituted alkylene, R ³ represents a hydrogen atom, a substituted or unsubstituted aryl, a substituted or unsubstituted aliphatic heterocyclic group or a substituted or unsubstituted aromatic heterocyclic group,
R ⁴ represents a substituted or unsubstituted aryl or a substituted or unsubstituted aromatic heterocyclic group>
Or a pharmacologically acceptable salt thereof. R ¹ and R ² are the same or different and are a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted C _1-10 alkyl, substituted or unsubstituted C _2-10 alkenyl, substituted or unsubstituted C _{2 -10} alkynyl, substituted or unsubstituted C _3-8 cycloalkyl, substituted or unsubstituted C _6-14 aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted Or unsubstituted C _1-10 alkoxy, —NR ^c R ^d , wherein R ^c and R ^d are the same or different and each represents a hydrogen atom, substituted or unsubstituted C _1-10 alkyl, substituted or unsubstituted C 1 _2-10 alkenyl, substituted or unsubstituted C _2-10 alkynyl, substituted or unsubstituted C _3-8 cycloalkyl, substituted or unsubstituted C _{6 -14} aryl, a substituted or unsubstituted aliphatic heterocyclic group or a substituted or unsubstituted aromatic heterocyclic group) or -COR ^5A [wherein R ^5A is hydroxy, substituted or unsubstituted C _1-10 Alkoxy, substituted or unsubstituted C _6-14 aryloxy, —NR ^cc R ^dd (wherein R ^cc and R ^dd are the same as R ^c and R ^d , respectively), an aliphatic heterocyclic group, or aromatic Represents a heterocyclic group], or R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocyclic ring,
(I) R ¹ and R ² are the same or different and are a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted C _1-10 alkyl, substituted or unsubstituted C _2-10 alkenyl, substituted or unsubstituted C _2-10 alkynyl, substituted or unsubstituted C _3-8 cycloalkyl, substituted or unsubstituted C _6-14 aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic ring A group, substituted or unsubstituted C _1-10 alkoxy, —NR ^c R ^d (wherein R ^c and R ^d are as defined above) or —COR ^5A (wherein R ^5A is as defined above); Is)
Y represents C _1-10 alkylene, R ³ represents a substituted or unsubstituted bicyclic heterocyclic group,
R ⁴ represents 2,3-dichlorophenyl,
(Ii) when R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocycle,
Y represents a substituted or unsubstituted C _1-10 alkylene, R ³ represents a hydrogen atom, a substituted or unsubstituted C _6-14 aryl, a substituted or unsubstituted aliphatic heterocyclic group, or a substituted or unsubstituted aromatic Represents a heterocyclic group,
The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein R ⁴ represents a substituted or unsubstituted C _6-14 aryl or a substituted or unsubstituted aromatic heterocyclic group. R ¹ and R ² are the same or different and are a hydrogen atom, halogen, cyano, nitro, substituted or unsubstituted C _1-10 alkyl, substituted or unsubstituted C _2-10 alkenyl, substituted or unsubstituted C _{2 -10} alkynyl, substituted or unsubstituted C _3-8 cycloalkyl, substituted or unsubstituted C _6-14 aryl, substituted or unsubstituted aliphatic heterocyclic group, substituted or unsubstituted aromatic heterocyclic group,- The sulfonamide derivative according to claim 2, or R ^5A (wherein R ^5A is as defined above) or -NR ^c R ^d (wherein R ^c and R ^d are as defined above) or Pharmacologically acceptable salt. The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein R ¹ and R ² are the same or different and are a hydrogen atom or a halogen. The bicyclic heterocyclic group is a heterocyclic group selected from the group consisting of benzodioxolyl, benzodioxinyl, dihydrobenzofuranyl, benzotriazolyl, benzofuryl, indolyl and imidazolyl. Any one of the sulfonamide derivatives or a pharmacologically acceptable salt thereof. The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein R ¹ and R ² together with adjacent carbon atoms form a substituted or unsubstituted aromatic heterocycle. . The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to claim 6, wherein the substituted or unsubstituted aromatic heterocyclic ring formed together with adjacent carbon atoms is pyridine. The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to claim 6 or 7, wherein R ³ is a substituted or unsubstituted C _6-14 aryl or a substituted or unsubstituted aromatic heterocyclic group. The sulfonamide derivative or a pharmaceutically acceptable salt thereof according to any one of claims 6 to 8, wherein R ⁴ is substituted or unsubstituted C _6-14 aryl. Sulfonamide derivative or a pharmacologically acceptable salt thereof according to any one of claims 6-8 R ⁴ is 2,3-dichlorophenyl. Y is methylene or ethylene, The sulfonamide derivative in any one of Claims 1-10, or its pharmacologically acceptable salt. Y is methylene, The sulfonamide derivative in any one of Claims 1-10, or its pharmacologically acceptable salt. The pharmaceutical which contains the sulfonamide derivative in any one of Claims 1-12, or its pharmacologically acceptable salt as an active ingredient. A thymus and activation-regulated chemokine (TARC; containing the sulfonamide derivative according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof as an active ingredient. CC chemokine ligand 17 (CCL17))] and / or macrophage-derived chemokine (MDC; CC chemokin ligand 22 (CCL22))]. A therapeutic and / or prophylactic agent for a disease involving TARC and / or MDC, comprising the sulfonamide derivative according to any one of claims 1 to 12 or a pharmacologically acceptable salt thereof as an active ingredient. A therapeutic and / or prophylactic agent for a disease involving T cells, comprising the sulfonamide derivative according to claim 1 or a pharmacologically acceptable salt thereof as an active ingredient.