Th2 differentiation inhibitors

A method for treating graft immune diseases (chronic GVHD), ulcerative colitis, systemic lupus erythematodes, myasthenia gravis, systemic progressive scleroderma, rheumatoid arthritis, interstitial cystitis, Hashimoto's diseases, Basedow's diseases, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, Goodpasture's syndrome, atrophic gastritis, pernicious anemia, Addison diseases, pemphigus, pemphigoid, lenticular uveitis, sympathetic ophthalmia, primary biliary cirrhosis, active chronic hepatitis, Sjogren's syndrome, multiple myositis, dermatomyositis, polyarteritis nodosa, rheumatic fever, glomerular nephritis, lupus nephritis, IgA nephtopathy, allergic encephalitis, atopic allergic diseases, bronchial asthma, airway inflammation, allergic rhinitis, allergic dermatitis, allergic conjunctivitis, pollinosis, urticaria, food allergy, Omenn's syndrome, vernal conjunctivitis or hypereosinophilic syndrome comprising inhibiting the differentiation from Th0 cells to Th2 cells by administering to a patient in need thereof a compound represented by Formula (Ib):

• wherein ring C is
• and the pyridine ring may be optionally substituted, each of R4, R5, R6, R7, R8, R9, R10, and R11 is independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, carboxy or lower alkoxycarbonyl;
• each of X1 and X2 is independently —O—, —CH2— or —NH—;
• each of Y1 and Y2 is independently optionally substituted lower alkyl, optionally substituted arylalkyl or optionally substituted lower alkenyl,
• or a prodrug, pharmaceutically acceptable salt or solvate thereof.

A method for treating graft immune diseases (chronic GVHD), ulcerative colitis, systemic lupus erythematodes, myasthenia gravis, systemic progressive scleroderma, rheumatoid arthritis, interstitial cystitis, Hashimoto's diseases, Basedow's diseases, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, Goodpasture's syndrome, atrophic gastritis, pernicious anemia, Addison diseases, pemphigus, pemphigoid, lenticular uveitis, sympathetic ophthalmia, primary biliary cirrhosis, active chronic hepatitis, Sjogren's syndrome, multiple myositis, dermatomyositis, polyarteritis nodosa, rheumatic fever, glomerular nephritis, lupus nephritis, IgA nephtopathy, allergic encephalitis, atopic allergic diseases, bronchial asthma, airway inflammation, allergic rhinitis, allergic dermatitis, allergic conjunctivitis, pollinosis, urticaria, food allergy, Omenn's syndrome, vernal conjunctivitis or hypereosinophilic syndrome comprising inhibiting the differentiation from Th0 cells to Th2 cells by administering to a patient in need thereof a compound represented by Formula (Ic):

• wherein each of ring A and ring B is independently an optionally substituted benzene ring;
• ring C is an optionally substituted pyridine ring;
• X1 is —O—, —CH2—, or —NH— and Y1 is optionally substituted lower alkyl, optionally substituted arylalkyl or optionally substituted lower alkenyl;
• X3 is —O— or —NH—;
• each of Ra and Rb is independently hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted acyl, optionally substituted lower alkoxycarbonyl or optionally substituted lower alkylsulfonyl, or they are taken together to form RcRdC═ or —(CReRf)s-;
• each of Rc and Rd is independently hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted lower alkoxy, optionally substituted lower alkylthio, optionally substituted lower alkenyloxy, optionally substituted lower alkynyloxy, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocyclyl or they are taken together with a carbon atom to which they are attached to form optionally substituted cycloalkylidene;
• each Re is independently hydrogen, lower alkyl, lower alkoxy or amino, and each Rf is independently hydrogen, lower alkyl, lower alkoxy or amino;
• n is an integer of 0 to 2 and s is an integer of 2 to 6, or a prodrug, pharmaceutically acceptable salt or solvate thereof.

A method for inhibiting the differentiation from Th0 cells to Th2 cells comprising administering to a patient in need thereof a compound represented by Formula (I):

• wherein each of ring A and ring B is independently an optionally substituted benzene ring;
• ring C is an optionally substituted pyridine ring wherein the substituent is halogen;
• hydroxy;
• lower alkyl which may be substituted by hydroxy or acyloxy;
• lower alkoxy which may be substituted by halogen, aryl or a 5- or 6-membered heterocyclic group;
• lower alkenyl;
• lower alkenyloxy;
• lower alkynyl;
• lower alkynyloxy;
• acyloxy;
• carboxy;
• lower alkoxycarbonyl;
• mercapto;
• lower alkylthio;
• lower alkenylthio;
• amino which may be mono- or di-substituted by halogen, optionally substituted lower alkyl (a substituent is cycloalkyl or a 5- or 6-membered heterocyclic group), optionally halogen-substituted acyl, lower alkenyl, cycloalkyl or lower alkylsulfonyl;
• imino which may be substituted by lower alkylsulfonyl;
• hydrazino which may be substituted by lower alkyl, lower alkenyl, optionally substituted lower alkylidene or cycloalkylidene;
• aminooxy which may be substituted by lower alkyl, lower alkenyl, optionally substituted lower alkylidene or cycloalkylidene;
• nitro;
• lower alkylsulfonyl;
• aryl;
• a 5- or 6-membered heterocyclic group;
• oxo;
• or oxide;
• X is —O—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl or lower alkylcarbonyl) or —S(O)-p-wherein p is an integer of 0 to 2;
• Y is hydrogen, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted acyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted sulfamoyl, optionally substituted amino, optionally substituted aryl, pyrrole, imidazole, pyrazole, pyridine, pyridazine, pyrimidine, pyrazine, triazole, triazine, isoxazole, oxazole, oxadiazole, isothiazole, thiazole, thiadiazole, furan, thiophene, tetrahydropyran, dihydropyridine, dihydropyridazine, dihydropyrazine, dioxane, oxathiolane, thiane, pyrrolidine, pyrroline, imidazolidine, imidazoline, pyrazolidine, pyrazoline, piperidine, or morpholine;
• R1 and Y taken together may form —(CH2)m—, —(CH2)2—T—(CH2)2— wherein T is O, S or NR′, —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, C (═O)—(CH2)r-, —C (═O)—NR′—(CH2)r- or —C(═O)—NR′—N═CH— wherein m is 4 or 5, r is 2 or 3 and R′ is hydrogen, lower alkyl or lower alkenyl;
• Y may be halogen when X is —NR1— and
• Y may be optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—;
• both V1 and V2 are single bonds or one of V1 and V2 is a single bond and the other is —O—, —NH—, —OCH2—, —CH2O—, —CH═CH—, —C≡C—, —CH(OR2)— wherein R2 is hydrogen or lower alkyl, —CO—, —NHCHR — or —CHR3NH— wherein R3 is hydrogen or hydroxy, or a prodrug, pharmaceutically acceptable salt or solvate thereof.

A method for inhibiting the differentiation from Th0 cells to Th2 cells comprising administering to a patient in need thereof a compound represented by Formula (Ib):

• wherein ring C is an optionally substituted
• and the pyridine ring may be optionally substituted, each of R4, R5, R6, R7, R8, R9, R10, and R11 is independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, carboxy or lower alkoxycarbonyl;
• each of X1 and X2 is independently —O—, —CH2— or —NH—;
• each of Y1 and Y2 is independently optionally substituted lower alkyl, optionally substituted arylalkyl or optionally substituted lower alkenyl, or a prodrug, pharmaceutically acceptable salt or solvate thereof.

A method for treating graft immune diseases (chronic GVHD), ulcerative colitis, systemic lupus erythematodes, myasthenia gravis, systemic progressive scleroderma, rheumatoid arthritis, interstitial cystitis, Hashimoto's diseases, Basedow's diseases, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, Goodpasture's syndrome, atrophic gastritis, pernicious anemia, Addison diseases, pemphigus, pemphigoid, lenticular uveitis, sympathetic ophthalmia, primary biliary cirrhosis, active chronic hepatitis, Sjogren's syndrome, multiple myositis, dermatomyositis, polyarteritis nodosa, rheumatic fever, glomerular nephritis, lupus nephritis, IgA nephtopathy, allergic encephalitis, atopic allergic diseases, bronchial asthma, airway inflammation, allergic rhinitis, allergic dermatitis, allergic conjunctivitis, pollinosis, urticaria, food allergy, Omenn's syndrome, vernal conjunctivitis or hypereosinophilic syndrome comprising inhibiting the differentiation from Th0 cells to Th2 cells by administering to a patient in need thereof a compound represented by Formula (Ib)

• wherein ring C is an optionally substituted pyridine ring, each of R4, R5, R6, R7, R8, R9, R10, and R11 is independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, carboxy or lower alkoxycarbonyl;
• each of X1 and X2 is independently —O— or —NH—;
• each of Y1 and Y2 is independently optionally substituted lower alkyl, optionally substituted arylalkyl or optionally substituted lower alkenyl,
• or a prodrug, pharmaceutically acceptable salt or solvate thereof.

A method for inhibiting the differentiation from Th0 cells to Th2 cells comprising administering to a patient in need thereof a compound represented by Formula (Ib):

• wherein ring C is an optionally substituted pyridine ring, each of R4, R5, R6, R7, R8, R9, R10, R11, and R11 is independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, carboxy or lower alkoxycarbonyl;
• each of X1 and X2 is independently —O— or —NH—;
• each of Y1 and Y2 is independently optionally substituted lower alkyl, optionally substituted arylalkyl or optionally substituted lower alkenyl,
• or a prodrug, pharmaceutically acceptable salt or solvate thereof.