Patent ID: 6916814
Filing Date: 2005-07-12
Classification: A61K,A61P

Abstract:
1. A method of treating a disease or condition chosen from: acute and chronic inflammation in the lung caused by inhalation of smoke, pancreatitis, percutaneous transluminal coronary angioplasty, chronic obstructive pulmonary disease and congestive heart failure, said method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of the formula (I): wherein Ar Ar phenyl, naphthyl, quinoline, isoquinoline, tetrahydronaphthyl, tetrahydroquinoline, tetrahydroisoquinoline, benzimidazole, benzofuran, indanyl, indenyl or indole each being optionally substituted with one to three R 2 groups; L is a C wherein one or more methylene groups are optionally independently replaced by O,N or S; and wherein said linking group is optionally substituted with 0-2 oxo groups and one or more C Q is selected from the group consisting of: a) pyridine, pyrimidine, pyridazine, imidazole, benzimidazole, oxazo[4,5-b]pyridine and imidazo[4,5-b]pyridine, which are optionally substituted with one to three groups selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 alkoxy, hydroxy, mono- or di-(C 1-3 alkyl)amino, C 1-6 alkyl-S(O) m and phenylamino wherein the phenyl ring is optionally substituted with one to two groups consisting of halogen, C 1-6 alkyl and C 1-6 alkoxy; b) morpholine, thiomorpholine, thiomorpholine sulfoxide, thiomorpholine sulfone, piperidine, piperidinone and tetrahydropyrimidone which are optionally substituted with one to three groups selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, hydroxy, mono- or di-(C 1-3 alkyl)amino-C 1-3 alkyl, phenylamino-C 1-3 alkyl and C 1-3 alkoxy-C 1-3 alkyl; R a) C 3-10 branched or unbranched alkyl, which may optionally be partially or fully halogenated, and optionally substituted with one to three phenyl, naphthyl or heterocyclic groups selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl; each such phenyl, naphthyl or heterocycle selected from the group hereinabove described, being substituted with 0 to 5 groups selected from the group consisting of halogen, C 1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, C 3-8 cycloalkyl, C 5-8 cycloalkenyl, hydroxy, cyano, C 1-3 alkyloxy which is optionally partially or fully halogenated, NH 2 C(O) and di(C 1-3 )alkylaminocarbonyl; b) C 3-7 cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, which may optionally be partially or fully halogenated and which may optionally be substituted with one to three C 1-3 alkyl groups, or an analog of such cycloalkyl group wherein one to three ring methylene groups are replaced by groups independently selected from O, S, CHOH, >C═O, >C═S and NH; c) C 3-10 branched alkenyl which may optionally be partially or fully halogenated, and which is optionally substituted with one to three C 1-5 branched or unbranched alkyl, phenyl, naphthyl or heterocyclic groups, with each such heterocyclic group being independently selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, and each such phenyl, naphthyl or heterocyclic group being substituted with 0 to 5 groups selected from halogen, C 1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, hydroxy, cyano, C 1-3 alkyloxy which is optionally partially or fully halogenated, NH 2 C(O), mono- or di(C 1-3 )alkylaminocarbonyl; d) C 5-7 cycloalkenyl selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group may optionally be substituted with one to three C 1-3 alkyl groups; e) cyano; and, f) methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl; R a C 1-6 branched or unbranched alkyl which may optionally be partially or fully halogenated, acetyl, aroyl, C 1-4 branched or unbranched alkoxy, which may optionally be partially or fully halogenated, halogen, methoxycarbonyl and phenylsulfonyl; R a) a phenyl, naphthyl or heterocyclic group selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl and indazolyl; wherein such phenyl, naphthyl or heterocyclic group is optionally substituted with one to five groups selected from the group consisting of a C 1-6 branched or unbranched alkyl, phenyl, naphthyl, heterocycle selected from the group hereinabove described, C 1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C 1-5 alkyl, naphthyl C 1-5 alkyl, halo, hydroxy, cyano, C 1-3 alkyloxy which may optionally be partially or fully halogenated, phenyloxy, naphthyloxy, heteraryloxy wherein the heterocyclic moiety is selected from the group hereinabove described, nitro, amino, mono- or di-(C 1-3 )alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinabove described, NH 2 C(O), a mono- or di-(C 1-3 )alkyl aminocarbonyl, C 1-5 alkyl-C(O)—C 1-4 alkyl, amino-C 1-5 alkyl, mono- or di-(C 1-3 )alkylamino-C 1-5 alkyl, amino-S(O) 2 , di-(C 1-3 )alkylamino-S(O) 2 , R 4 —C 1-5 alkyl, R 5 —C 1-5 alkoxy, R 6 —C(O)—C 1-5 alkyl and R 7 —C 1-5 alkyl(R 8 )N; b) a fused aryl selected from the group consisting of benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, or a fused heterocyclyl selected from the group consisting of cyclopentenopyridine, cyclohexanopyridine, cyclopentanopyrimidine, cyclohexanopyrimidine, cyclopentanopyrazine, cyclohexanopyrazine, cyclopentanopyridazine, cyclohexanopyridazine, cyclopentanoquinoline, cyclohexanoquinoline, cyclopentanoisoquinoline, cyclohexanoisoquinoline, cyclopentanoindole, cyclohexanoindole, cyclopentanobenzimidazole, cyclohexanobenzimidazole, cyclopentanobenzoxazole, cyclohexanobenzoxazole, cyclopentanoimidazole, cyclohexanoimidazole, cyclopentanothiophene and cyclohexanothiophene; wherein the fused aryl or fused heterocyclyl ring is substituted with 0 to 3 groups independently selected from phenyl, naphthyl and heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, and isothiazolyl, C 1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, halo, cyano, C 1-3 alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heterocyclyloxy wherein the heterocyclyl moiety is selected from the group hereinabove described, nitro, amino, mono- or di-(C 1-3 )alkylamino, phenylamino, naphthylamino, heterocyclylamino wherein the heterocyclyl moiety is selected from the group hereinaboved described, NH 2 C(O), a mono- or di-(C 1-3 )alkyl aminocarbonyl, C 1-4 alkyl-OC(O), C 1-5 alkyl-C(O)—C 1-4 branched or unbranched alkyl, an amino-C 1-5 alkyl, mono- or di-(C 1-3 )alkylamino-C 1-5 alkyl, R 9 —C 1-5 alkyl, R 10 —C 1-5 alkoxy, R 11 —C(O)—C 1-5 alkyl and R 12 —C 1-5 alkyl(R 13 )N; c) cycloalkyl selected from the group consisting of cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, which the cycloalkyl may optionally be partially or fully halogenated and which may optionally be substituted with one to three C 1-3 alkyl groups; d) C 5-7 cycloalkenyl, selected from the group consisting of cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein such cycloalkenyl group may optionally be substituted with one to three C 1-3 alkyl groups; and e) acetyl, aroyl, alkoxycarbonylalkyl or phenylsulfonyl; f) C 1-6 branched or unbranched alkyl which may optionally be partially or fully halogenated; wherein or R 1 and R 2 taken together may optionally form a fused phenyl or pyridinyl ring, each R hydrogen and C 1-4 branched or unbranched alkyl which may optionally be partially or fully halogenated; each R morpholine, piperidine, piperazine, imidazole and tetrazole; m=0, 1, 2; r=0, 1, 2; t=0, 1, 2; and X=O or S or the physiologically acceptable acids or salts thereof.