Compounds useful as anti-inflammatory agents

A Compound of the formula (I):

• wherein:
• G is:
• pyridinyl substituted by one or more R1, R2 or R3;
• Ar is:
• naphthyl, tetrahydronaphthyl, indanyl, or indenyl each optionally substituted by one or more R4 or R5 groups;
• L is a:
• O, NH, CH2 or S(O)m, O—CH2—, O—CH2CH2, O—CH2CH2CH2, O—CH2CH2(CH3), O—CH2(CH3)CH2, NHCH2, NHCH2CH2, NHCH2CH2CH2, S(O)mCH2, S(O)mCH2CH2, S(O)mCH2CH2CH2, CH2CH2, CH2CH2CH2, O—CH2C(O), HC≡C—CH2 or HC≡C—CH2O
• Q is:
• pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, benzimidazolyl, furanyl, thienyl, pyranyl, naphthyridinyl, pyrazinyl, pyrazolyl, triazolyl, tetrazolyl, pyrazolo[3,4-b]pyrimidinyl, purinyl, pyrrolo[2,3-b]pyridinyl, pyrazolo[3,4-b]pyridinyl, tubercidinyl, oxazo[4,5-b]pyridinyl and imidazo[4,5-b]pyridinyl, which are optionally substituted with one to three C1-6 alkyl, C1-6 alkoxy, hydroxy, amino, mono- or di-(C1-3 alkyl)amino, mono- or di-(phenyl-C1-3 alkyl)amino, C1-6 alkyl-S(O)m, phenyl-C1-3-alkoxy or phenylamino wherein the phenyl ring is optionally substituted with one to two halogen, C1-6 alkyl or C1-6 alkoxy;
• tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanone, 1,3-dioxanone, 1,4-dioxanyl, morpholino, thiomorpholino, thiomorpholino sulfoxide, thiomorpholino sulfone, piperazinyl, piperidinyl, piperidinonyl, tetrahydropyrimidonyl, pentamethylene sulfide, pentamethylene sulfoxide, pentamethylene sulfone, tetramethylene sulfide, tetramethylene sulfoxide or tetramethylene sulfone which are optionally substituted with one to three C1-6 alkyl, C1-6 alkoxy, hydroxy, mono- or di-(C1-3 alkyl)amino-C1-3 alkyl, phenylamino-C1-3 alkyl or C1-3 alkoxy-C1-3 alkyl;
• each R1 is independently:
• C3-10 branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with one to three C3-10 cycloalkyl, hydroxy, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl each optionally substituted with 1 to 5 halogen, C1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, C3-8 cycloalkyl, C5-8 cycloalkenyl, hydroxy, cyano, C1-3 alkoxy which is optionally partially or fully halogenated and NH2C(O) or mono- or di(C1-3)alkylaminocarbonyl;
• cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, which are optionally partially or fully halogenated and optionally substituted with one to three C1-3 alkyl groups optionally partially or fully halogenated, cyano, hydroxyC1-3alkyl or aryl;
• or an analog of cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl wherein one to three ring methylene groups are replaced independently by O, S(O)m, CHOH, >C═O, >C═S or NH;
• C3-10 branched or unbranched alkenyl optionally partially or fully halogenated, and optionally substituted with one to three C1-5 branched or unbranched alkyl, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl, each optionally substituted with 1 to 5 halogen, C1-6 branched or unbranched alkyl optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, hydroxy, cyano, C1-3 alkoxy optionally partially or fully halogenated, NH2C(O) or mono- or di(C1-3)alkylaminocarbonyl;
• the C3-10 branched or unbranched alkenyl is optionally interrupted by one or more O, N or S(O)m;
• cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, each optionally substituted with one to three C1-3 alkyl groups;
• cyano, halogen;
• methoxycarbonyl, ethoxycarbonyl or propoxycarbonyl;
• silyl containing three C1-4 independently branched or unbranched alkyl groups optionally partially or fully halogenated;
• C2-6 branched or unbranched alkyl-C(O), C2-6 branched or unbranched-S, C2-6 branched or unbranched-S(O), C2-6 branched or unbranched-S(O)2;
• C2-6 alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH and S(O)m and wherein said alkynyl group is optionally independently substituted with 0-2 oxo groups, pyrroldinyl, pyrrolyl, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, nitrile, morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl, or C1-4 branched or unbranched alkylamino optionally substituted by one or more halogen atoms;
• each R2, R4, and R5 is independently
• a C1-6 branched or unbranched alkyl optionally partially or fully halogenated, acetyl, aroyl, C1-4 branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl or phenylsulfonyl;
• C1-6 alkoxy, hydroxy, amino, or mono- or di-(C1-4 alkyl)amino, cyano, halogen;
• OR6;
• nitro;
• or
• mono- or di-(C1-4 alkyl)amino-S(O)2 optionally partially or fully halogenated, or H2NSO2;
• each R3 is independently:
• hydrogen, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thienyl, furyl, tetrahydrofuryl, isoxazolyl, thiazolyl, oxazolyl, triazolyl, tetrazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl or indazolyl each optionally substituted with one to five phenyl, naphthyl, heterocycle or heteroaryl wherein the heterocyclic and heteraryl moiety is as hereinabove described in this paragraph, C1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C1-5 alkyl, naphthyl C1-5 alkyl, halogen, hydroxy, oxo, cyano, C1-3 alkoxy optionally partially or fully halogenated, phenyloxy, naphthyloxy, heteraryloxy wherein the heterocyclic moiety is as hereinabove described in this paragraph, nitro, amino, mono- or di-(C1-3)alkylamino, phenylamino, naphthylamino, heterocyclic or heteroaryl amino wherein the heterocyclic or heteroaryl moiety is as hereinabove described in this paragraph, NH2C(O), a mono- or di-(C1-3)alkyl aminocarbonyl, C1-5 alkyl-C(O)—C1-4 alkyl, amino-C1-5 alkyl, mono- or di-(C1-3)alkylamino-C1-5 alkyl, amino-S(O)2, di-(C1-3)alkylamino-S(O)2, R7—C1-5 alkyl, R8—C1-5 alkoxy, R9—C(O)—C1-5 alkyl, R10—C1-5 alkyl(R11)N, carboxy-mono- or di-(C1-5)-alkyl-amino;
• a fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, or a fused heterocycle selected from 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 heterocyclic ring is optionally independently substituted with 1 to 3 groups selected from phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, isothiazolyl, C1-6 branched or unbranched alkyl optionally partially or fully halogenated, halo, cyano, C1-3 alkoxy optionally partially or fully halogenated, phenyloxy, naphthyloxy, heterocyclicoxy heteroaryloxy wherein the heterocyclic or heteroaryl moiety is as hereinabove described in this paragraph, nitro, amino, mono- or di-(C1-3)alkylamino, phenylamino, naphthylamino, heterocyclicamino or heteroarylamino wherein the heterocyclic or heteroaryl moiety is as hereinabove described in this paragraph, NH2C(O), a mono- or di-(C1-3)alkyl aminocarbonyl, C1-4 alkyl-OC(O), C1-5 alkyl-C(O)—C1-4 branched or unbranched alkyl, an amino-C1-5 alkyl, mono- or di-(C1-3)alkylamino-C1-5 alkyl, R12—C1-5 alkyl, R13—C1-5 alkoxy, R14—C(O)—C1-5 alkyl and R15—C1-5 alkyl(R16)N;
• cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl optionally partially or fully halogenated and optionally substituted with one to three C1-3 alkyl groups, or an analog of cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl wherein one to three ring methylene groups are replaced independently by O, S(O)m, CHOH, >C═O, >C═S or NH;
• cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl each optionally substituted with one to three C1-3 alkyl groups;
• C1-4 branched or unbranched alkyl-phenyl-C(O)—C1-4 branched or unbranched alkyl, C1-4 branched or unbranched alkyl-C(O)—C1-4 branched or unbranched alkyl, C1-4 branched or unbranched alkyl-phenyl-S(O)m—C1-4 branched or unbranched alkyl;
• C1-6 branched or unbranched alkyl or C1-6 branched or unbranched alkoxy each is optionally partially or fully halogenated or optionally substituted with R17;
• C1-6 branched or unbranched alkyl optionally substituted with OR18;
• amino or C1-C5 branched or unbranched mono- or di-alkylamino optionally substituted with R19;
• cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy or cycloheptyloxy which are optionally partially or fully halogenated and optionally substituted with one to three C1-3 alkyl groups optionally partially or fully halogenated, wherein one to three ring methylene groups are replaced independently by O, S(O)m, CHOH, >C═O, >C═S or NH;
• R20C(O)N(R21)—, R22O— or R23R24NC(O)—;
• R26(CH2)mC(O)N(R21)— or R26C(O)(CH2)mN(R21)—;
• C2-6alkenyl substituted by R23R24NC(O)—;
• C2-6 alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH, S(O), S(O)2 or S and wherein said alkynyl group is optionally independently substituted with 0-2 oxo groups, pyrroldinyl, pyrrolyl, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, nitrile, morpholino, piperidine, piperazine, imidazole, phenyl, pyridine, tetrazole, or C1-4 branched or unbranched alkylamino optionally substituted by one or more halogen atoms;
• or
• aroyl;
• R6 is a:
• C1-4 branched or unbranched alkyl optionally partially or fully halogenated and optionally substituted with R26;
• each R7, R8, R9, R10, R12, R13, R14, R15, R17, R19, R25 and R26 is independently:
• nitrile, morpholino, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl or alkylamino mono- or di-C1-4 branched or unbranched optionally partially or fully halogenated;
• each R11 and R16 is independently:
• hydrogen or C1-4 branched or unbranched alkyl optionally partially or fully halogenated;
• R18 is independently:
• hydrogen or a C1-4 branched or unbranched alkyl optionally independently substituted with oxo or R25;
• R20 is:
• C1-10 branched or unbranched alkyl optionally partially or fully halogenated, phenyl or pyridinyl;
• R21 is:
• hydrogen or C1-3 branched or unbranched alkyl optionally partially or fully halogenated;
• each R22, R23 and R24 is independently:
• hydrogen, C1-6 branched or unbranched alkyl optionally substituted by carbonylamino-mono- or di-C1-3alkyl or amino-mono or diC1-3alkyl or wherein said C1-6 alkyl optionally partially or fully halogenated and optionally interrupted by one or more O, N or S, phenyl, pyridine or alkylamino;
• or R23 and R24 taken together optionally form a heterocyclic or heteroaryl ring;
• m=0, 1 or 2;
• X=O or S;
• and
• the pharmaceutically acceptable derivatives thereof.