Patent ID: 6689804
Filing Date: 2004-02-10
Classification: A61P,C07D,C07F,Y02P

Abstract:
A method for the treatment of an inflammatory condition which comprises administering to a host in need or such treatment is a therapeutic amount of a compound of the formula I, wherein:A1 is &boxH;Nâ€”; A2 is &boxH;C(H)â€”; D is &boxH;C(SO2R1)â€”, wherein R1 is selected from the group consisting of: (A) â€”R100e, which is: â€ƒbranched or unbranched alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms or cycloalkyl or cycloalkenyl of 3 to 6 carbon atoms, in which alkyl, alkenyl, cycloalkyl or cycloalkenyl group one or more hydrogen atoms are optionally and independently replaced with: (i) oxo, (ii) a group of the formula â€”COOR18, wherein R18 is straight or branched alkyl of 1 to 7 carbon atoms or cycloalkyl of 3 to 6 carbon atoms, (iii) a group of the formula â€”CONR19R20, wherein R19 and R20 are each, independently, a hydrogen atom, alkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 6 carbon atoms, or wherein R19 and R20 constitute a saturated hydrocarbon bridge of 3 to 5 carbon atoms which together with the nitrogen atom between them form a heterocyclic ring, and wherein one carbon atom in said hydrocarbon bridge is optionally replaced by â€”Oâ€”, â€”NHâ€”, or â€”NMeâ€”, (iv) a group of the formula â€”OR21, wherein R21 is a hydrogen atom, or a straight or branched alkyl or acyl group of 1 to 7 carbon atoms, wherein one or more hydrogen atoms of said alkyl or acyl group are optionally replaced with a group independently selected from the group consisting of â€”OH, â€”Oalkyl (wherein the alkyl moiety contains 1 to 6 carbon atoms), â€”NH2, â€”NHMe and â€”NMe2, or (v) a group of the formula â€”NR23R24, wherein R23 and R24 are each, independently, (a) a hydrogen atom, (b) straight or branched alkyl or acyl of 1 to 7 carbon atoms or cycloalkyl of 3 to 7 carbon atoms, wherein said one or more hydrogen atoms of said alkyl or acyl group are optionally replaced with a group independently selected from the group consisting of â€”OH, â€”Oalkyl (wherein the alkyl moiety is 1 to 6 carbon atoms), â€”NH2, â€”NHMe and â€”NMe2, (c) a group of the formula â€”CH2)mCOOH, wherein m is 0, 1 or 2, (d) a group of the formula â€”CH2)nCOOR25, wherein n is 0, 1 or 2, and wherein R25 is straight or branched alkyl of 1 to 6 carbon atoms, or (e) a group of the formula â€”CH2)nCONHR25, wherein n is 0, 1 or 2, and wherein R25 is straight or branched alkyl of 1 to 6 carbon atoms, (B) groups of the formula â€”NR46R47, wherein R46 and R47 are each independently a hydrogen atom, phenyl which is optionally monosubstituted with halogen, or R100e, wherein R100e is as hereinbefore defined, and (C) saturated or unsaturated heterocyclic groups selected from the group consisting of pyrrolinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl, wherein said heterocyclic groups are optionally mono- or poly-substituted with moieties independently selected from the group consisting of: (i) oxo, (ii) â€”OR101, wherein R101 is: (a) a hydrogen atom, (b) alkyl of 1 to 7 carbons, wherein any hydrogen atom of said alkyl group is optionally replaced with â€”OH, â€”OR110 (wherein R110 is an alkyl moiety of 1 to 6 carbon atoms), â€”NH2, â€”NHMe or â€”NMe2, (c) acyl of 1 to 7 carbons, wherein any hydrogen atom of said acyl group is optionally replaced with â€”OH, â€”OR111 (wherein R111 is an alkyl moiety of 1 to 6 carbon atoms), â€”NH2, â€”NHMe or â€”NMe2, (d) â€”CONR102R103, wherein R102 and R103 are each independently a hydrogen atom or alkyl of 1 to 7 atoms, or wherein R102 and R103 constitute a saturated hydrocarbon bridge of 3 to 5 carbon atoms which together with the nitrogen atom between them form a heterocyclic ring, and wherein one carbon atom in said hydrocarbon bridge is optionally replaced by â€”Oâ€”, â€”NHâ€”, or â€”NMeâ€”, or (e) â€”COOR104, wherein R104 is alkyl of 1 to 7 atoms, (iii) â€”CONR105R106, wherein R105 and R106 are each independently: (a) a hydrogen atom, or (b) straight or branched alkyl of 1 to 7 atoms or cycloalkyl of 3 to 7 atoms, â€ƒor, wherein R105 and R106 constitute a saturated hydrocarbon bridge of 3 to 5 carbon atoms which together with the nitrogen atom between them form a heterocyclic ring, and wherein one carbon atom in said hydrocarbon bridge is optionally replaced by â€”Oâ€”, â€”NHâ€”, or â€”NMeâ€”, (iv) â€”COOR107, wherein R107 is a hydrogen atom, or straight or branched alkyl of 1 to 7 carbon atoms, (v) straight or branched alkyl of 1 to 7 carbon atoms, alkenyl or alkynyl of 2 to 7 carbon atoms, or cycloalkyl of 3 to 7 carbons, wherein one or more hydrogen atoms of said alkyl, alkenyl, alkynyl or cycloalkyl group is optionally replaced with a moiety independently selected from the group consisting of: (a) oxo, (b) â€”OH, (c) â€”OR113, wherein R113 is alkyl of 1 to 6 carbon atoms, (d) â€”OCOCH3, (e) â€”NH2, (f) â€”NHMe, (g) â€”NMe2, (h) â€”CO2H, and (i) â€”CO2R114 wherein R114 is alkyl of 1 to 3 carbon atoms, or cycloalkyl of 3 to 7 carbons, (vi) acyl of 1 to 7 carbon atoms, which may be straight, branched or cyclic, and wherein one or more hydrogen atoms of said acyl group is optionally replaced with a moiety independently selected from the group consisting of: (a) â€”OH, (b) â€”OR115, wherein R115 is alkyl of 1 to 6 carbon atoms, (c) â€”NH2, (d) â€”NHMe, (e) â€”NMe2, (f) â€”NHCOMe, (g) oxo, (h) â€”CO2R116, wherein R116 is alkyl of 1 to 3 carbon atoms, (i) â€”CN, (j) the halogen atoms, (k) heterocycles selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl, and (l) aryl or heteroaryl selected from the group consisting of phenyl, thiophenyl, pyridyl, pyrimidinyl, furyl, pyrrolyl and oxazolyl, (vii) â€”SO2R108, wherein R108 is: (a) phenyl, wherein said phenyl moiety is optionally substituted with one or more moieties selected from the group consisting of the halogen atoms, straight or branched alkyl of 1 to 6 carbons, and â€”OR117 (wherein R117 is hydrogen or alkyl of 1 to 6 carbon atoms), (b) a heterocyclic group selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl, wherein said heterocyclic group is optionally substituted with one or more moieties selected from the group consisting of the halogen atoms, straight or branched alkyl of 1 to 6 carbons, and â€”OR118 (wherein R118 is hydrogen or alkyl of 1 to 6 carbon atoms), or (c) straight or branched alkyl of 1 to 7 atoms, wherein said alkyl moiety is optionally substituted with one or more moieties selected from the group consisting of the halogen atoms, straight or branched alkyl of 1 to 6 carbons, and â€”OR119 (wherein R119 is hydrogen or alkyl of 1 to 6 carbon atoms), (viii) â€”COR109, wherein R109 is: (a) phenyl, wherein said phenyl moiety is optionally substituted with one or more moieties selected from the group consisting of the halogen atoms, straight or branched alkyl of 1 to 6 carbons, and â€”OR120 (wherein R120 is hydrogen or alkyl of 1 to 6 carbon atoms), (b) a heterocyclic group selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl, wherein said heterocyclyl is optionally substituted with one or more halogen, straight or branched alkyl of 1 to 6 carbons, or â€”OR121 (wherein R121 is hydrogen or alkyl of 1 to 6 carbon atoms), or (c) straight or branched alkyl of 1 to 7 atoms, wherein said alkyl moiety is optionally substituted with one or more moieties selected from the group consisting of the halogen atoms, straight or branched alkyl of 1 to 6 carbons, and â€”OR122 (wherein R122 is hydrogen or alkyl of 1 to 6 carbon atoms), and (ix) â€”CHO; X is an oxygen atom; R3 is branched or unbranched alkyl of 1 to 3 carbon atoms; R4 is a group of the formula â€”CH2R55, wherein, R55 is: â€ƒphenyl, which is optionally substituted at the 4-position with: (A) R59e, which is aryl or heteroaryl selected from the group consisting of phenyl, thiophenyl, pyridyl, pyrimidinyl and furyl, wherein one of the hydrogen atoms of said aryl or heteroaryl group is optionally replaced with: (i) methyl, (ii) â€”CN, (iii) nitro, or (iv) halogen, (B) methyl, (C) â€”CN, (D) nitro, or (E) halogen; R5 is Cl; Z is &boxH;C(H)â€”; and, R7 is Cl; or a pharmaceutically acceptable salt thereof.