Patent ID: 6566385
Filing Date: 2003-05-20
Classification: A61P,C07D

Abstract:
A compound of the formula A1: wherein:R1a, R1b, R1d and R1e are independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C1-C6 perfluoroalkyl, R10Oâ€”, R11S(O)mâ€”, R10C(O)NR10â€”, (R10)2Nâ€”C(O)â€”, CN, NO2, (R10)2Nâ€”C(NR10)â€”, (R10)2Nâ€”C(O)NR10â€”, R10C(O)â€”, R10OC(O)â€”, â€”N(R10)2, or R10OC(O)NR10â€”, c) unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl or unsubstituted or substituted C2-C6 alkynyl, wherein the substituent on the substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2â€”C6 alkynyl is selected from unsubstituted or substituted aryl, heterocyclic, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, halogen, R10Oâ€”, R4S(O)mâ€”, R4S(O)2NR10â€”, R10C(O)NR10â€”, (R10)2Nâ€”C(O)â€”, CN, (R10)2Nâ€”C(NR10)â€”, R10C(O)â€”, R10OC(O)â€”, â€”N(R10)2, and R11OC(O)â€”NR10â€”; or two R1as, two R1bs or two R1es, on the same carbon atom may be combined to form â€”(CH2)vâ€”, wherein one of the CH2 moieties is optionally replaced with â€”C(&boxH;O)â€”, â€”NHâ€” or â€”NHC(&boxH;O)â€”;R4 is selected from C1-4 alkyl, C3-6 cycloalkyl, heterocycle, aryl, unsubstituted or substituted with: a) C1-4 alkoxy, b) aryl or heterocycle, c) halogen, d) HO, e) f) â€”SO2R11, g) N(R10)2, or h) C1-4 perfluoroalkyl; R6 and R7 are independently selected from: 1) hydrogen, 2) R10C(O)â€”, or R10OC(O)â€”, and 3) C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-6 cycloalkyl, heterocycle, aryl, aroyl, heteroaroyl, arylsulfonyl, heteroarylsulfonyl, unsubstituted or substituted with one or more substituents selected from: a) R10Oâ€”, b) aryl or heterocycle, c) halogen, d) R10C(O)NR10â€”, e) f) â€”SO2R11, g) N(R10)2, h) C3-6 cycloalkyl, i) C1-C6 perfluoroalkyl, j) (R10)2Nâ€”C(NR10)â€”, k) R10OC(O)â€”, l) R11OC(O)NR10â€”, m) CN, and n) NO2, or R6 and R7 may be joined in a ring; R8 is independently selected from: a) hydrogen, b) unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Br, R12Oâ€”, R11S(O)mâ€”, R10C(O)NR10â€”, (R10)2NC(O)â€”, R102Nâ€”C(NR10)â€”, CN, NO2, R10C(O)â€”, R10OC(O)â€”, â€”N(R10)2, or R11OC(O)NR10â€”, and c) C1-C6 alkyl unsubstituted or substituted by unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Br, R10O, R11S(O)mâ€”, R10C(O)NHâ€”, (R10)2NC(O)â€”, R10)2Nâ€”C(NR10)â€”, CN, R10C(O)â€”, R10OC(O)â€”, â€”N(R10)2, or R10OC(O)NHâ€”; R9 is selected from: a) hydrogen, b) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 perfluoroalkyl, F, Cl, Br, R10Oâ€”, R11S(O)mâ€”, R10C(O)NR10â€”, (R10)2NC(O)â€”, R10)2NC(NR10)â€”, CN, NO2, R10C(O)â€”, R10OC(O)â€”, â€”N(R10)2, or R11OC(O)NR10â€”, and c) C1-C6 alkyl unsubstituted or substituted by C1-C6 perfluoroalkyl, F, Cl, Br, R10Oâ€”, R11S(O)mâ€”, R10C(O)NR10â€”, (R10)2NC(O)â€”, R102NC(NR10)â€”, CN, R10C(O)â€”, R10OC(O)â€”, â€”N(R10)2, or R11OC(O)NR10â€”; R10 is independently selected from hydrogen, C1-C6 alkyl, unsubstituted or substituted benzyl, unsubstituted or substituted aryl and unsubstituted or substituted heterocycle; R11 is independently selected from C1-C6 alkyl unsubstituted or substituted aryl and unsubstituted or substituted heterocycle; R12 is independently selected from hydrogen, C1-C6 alkyl, C1-C3 perfluoroalkyl, unsubstituted or substituted benzyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycle, and C1-C6 alkyl substituted with unsubstituted or substituted aryl or unsubstituted or substituted heterocycle; A1 is O; W is imidazolyl; V is phenyl; X is selected from â€”C(O)â€”, â€”C(O)NR10â€”, â€”NR10C(O)â€”, â€”NR10C(O)â€”Oâ€”, â€”Oâ€”C(O)NR10â€”, â€”NR10C(O)NR10â€”, O, â€”N(R10)â€”, â€”S(O)2N(R10)â€”, â€”N(R10)S(O)2â€” and S(O)m; Z1 is unsubstituted or substituted phenyl or unsubstituted or substituted naphthyl, wherein the substituted phenyl or naphthyl is substituted with one or more of: 1) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl, unsubstituted or substituted with: a) C1-4 alkoxy, b) NR6R7, c) C3-6 cycloalkyl, d) aryl or heterocycle, e) HO, f) â€”S(O)mR4, g) â€”C(O)NR6R7, or h) C1-4 perfluoroalkyl; 2) substituted or unsubstituted aryl or substituted or unsubstituted heterocycle, 3) halogen, 4) OR6, 5) NR6R7, 6) CN, 7) NO2, 8) CF3, 9) â€”S(O)mR4, 10) â€”OS(O)2R4, 11) â€”C(O)NR6R7, 12) â€”C(O)OR6, or 13) C3-C6 cycloalkyl; heterocycle or heterocyclic represents a stable 5- to 7-membered monocyclic or stable 8- to 11-membered bicyclic heterocyclic ring which is either saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O, and S, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring; substituted aryl, heterocycle and benzyl include moieties containing from 1 to 3 substituents, in addition to the point of attachment to the rest of the compound, said substituents selected from F, Cl, Br, CF3, NH2, N(C1-C6 alkyl)2, NO2, CN, (C1-C6 alkyl)Oâ€”, (aryl)Oâ€”, â€”OH, (C1-C6 alkyl)S(O)mâ€”, (C1-C6 alkyl)C(O)NHâ€”, H2Nâ€”C(NH)â€”, (C1-C6 alkyl)C(O)â€”, (C1-C6 alkyl)OC(O)â€”, N3, (C1-C6 alkyl)OC(O)NHâ€”, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, isothiazolyl and C1-C20 alkyl; m is 0, 1 or 2; n is 0; p is 0 or 1; q is 1 or 2; r is 0 to 5; s is independently 0, 1, 2 or 3; t is 1, 2, 3, 4, 5, 6 or 7; and v is 2 to 6; or a pharmaceutically acceptable salt or stereoisomer thereof.