Patent ID: 6492520
Filing Date: 2002-12-10
Classification: A61P,C07D

Abstract:
A compound of the formula the dashed lines represent optional double bonds; A is CR7; B is â€”NR1R2, â€”CR1R2R10, â€”C(&boxH;CR2R11)R1, â€”NHCR1R2R10, â€”OCR1R2R10, â€”SCR1R2R10, â€”CR2R10NHR1, â€”CR2R10OR1, â€”CR2R10SR1 or â€”COR2, and is single bonded to D; or B is â€”CR1R2, and is double bonded to D and D is carbon; D is nitrogen or CR4 and is single bonded to all atoms to which it is attached, or D is carbon and is double bonded to E or double bonded to B; E is nitrogen, C&boxH;O, C&boxH;S, CR6R12, NR6 or CR6; K and G are each, independently, C&boxH;O, C&boxH;S, CHR8 or NR8 when single bonded to both adjacent ring atoms, or nitrogen or CR8 when it is double bonded to an adjacent ring atom; the 6-membered ring that contains D, E, K and G may contain from one to three double bonds; with the proviso that one of D, E, K, and G comprises a nitrogen atom that is a member of the 6-membered ring containing D,E, K and G, and the remaining of D, E, K, and G comprise carbon atoms that are each members of said 6-membered ring; R1 is C1-C6 alkyl optionally substituted with from one or two substituents independently selected from hydroxy, fluoro, chloro, bromo, iodo, C1-C4 alkoxy, CF3, â€”C(&boxH;O)(Câ€”C4alkyl), â€”C(&boxH;O)â€”Oâ€”(C1-C4)alkyl, â€”OC(&boxH;O)(C1-C4 alkyl), â€”OC(&boxH;O)N(C1-C4 alkyl)(C1-C2 alkyl), â€”NHCO(C1-C4 alkyl), â€”COOH, â€”COO(C1-C4 alkyl), â€”CONH(C1-C4 alkyl), â€”CON(C1-C4 alkyl)(C1-C2 alkyl), â€”S(C1-C4 alkyl), â€”CN, â€”NO2, â€”SO(C1-C4 alkyl), â€”SO2(C1-C4 alkyl), â€”SO2NH(C1-C4 alkyl) and â€”SO2N(C1-C4 alkyl)(C1-C2 alkyl), wherein each of the C1-C4 alkyl groups in the foregoing R1 groups may optionally contain one or two double or triple bonds; R2 is C1-C12 alkyl which may optionally contain from one to three double or triple bonds, aryl or (C1-C4 alkylene)aryl, wherein said aryl and the aryl moiety of said (C1-C4 alkylene)aryl is selected from phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl, isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridyl, oxazolyl and benzoxazolyl; C3-C8 cycloalkyl or (C1-C6 alkylene)(C3-C8 cycloalkyl), wherein one or two of the carbon atoms of said cycloalkyl and the 5 to 8 membered cycloalkyl moieties of said (C1-C6 alkylene)(C3-C8 cycloalkyl may optionally and independently be replaced by an oxygen or sulfur and wherein each of the foregoing R2 groups may optionally be substituted with from one to three substituents independently selected from chloro, fluoro, hydroxy and C1-C4 alkyl, or with one substituent selected from C1-C6 alkoxy, â€”OC(&boxH;O)(C1-C6 alkyl), â€”OC(&boxH;O)N(C1-C4 alkyl)(C1-C2 alkyl), â€”S(C1-C6 alkyl), amino, â€”NH(C1-C2 alkyl), â€”N(C1-C2 alkyl)(C1-C4 alkyl), â€”N(C1-C4 alkyl)â€”COâ€”(C1-C4 alkyl), â€”NHCO(C1-C4 alkyl), â€”COOH, â€”COO(C1-C4 alkyl), â€”CONH(C1-C4 alkyl), â€”CON(C1-C4 alkyl)(C1-C2 alkyl), â€”SH, â€”CN, â€”NO2, â€”SO(C1-C4 alkyl), â€”SO2(C1-C4 alkyl), â€”SO2NH(C1-C4 alkyl) and â€”SO2N(C1-C4 alkyl)(C1-C2 alkyl); â€”NR1R2 or CR1R2R10 may form a ring selected from saturated 3 to 8 membered rings, the 5 to 8 membered rings of which may optionally contain one or two double bonds, and wherein one or two of the ring carbon atoms of such 5 to 8 membered rings may optionally and independently be replaced by an oxygen or sulfur atom or by NZ3 wherein Z3 is hydrogen or C1-C4 alkyl; R3 is hydrogen, C1-C4 alkyl, â€”O(C1-C4 alkyl), chloro, fluoro, bromo, iodo, â€”S(C1-C4 alkyl) or â€”SO2(C1-C4 alkyl); R4 is hydrogen, C1-C2 alkyl, hydroxy or fluoro; each R6, R8 and R9 that is attached to a carbon atom is selected, independently, from hydrogen, C1-C2 alkyl, fluoro, chloro, bromo, iodo, hydroxy, hydroxymethyl, formyl, trifluoromethyl, cyano, amino, nitro, â€”O(C1-C2 alkyl), â€”N(C1-C2 alkyl)(C1-C2 alkyl), â€”S(C1-C2 alkyl), â€”CO(C1-C2 alkyl), â€”C(&boxH;O)H or â€”C(&boxH;O)O(C1-C2 alkyl), wherein each of the C1-C2 alkyl moieties in the foregoing R6, R8, and R9 groups may optionally contain one double or triple bond; and each R6, R8, and R9 that is attached to a nitrogen atom is selected, independently, from hydrogen and C1-C4 alkyl; R5 is substituted phenyl, naphthyl, pyridyl or pyrimidyl, wherein each of the foregoing R5 groups is substituted with from two to four substituents R15, wherein from one to three of said substituents may be selected, independently, from chloro, C1-C6 alkyl, â€”O(C1-C6 alkyl) and â€”(C1-C6alkylene)O(C1-C6alkyl), and wherein one of said substituents may be selected, independently, from bromo, iodo, formyl, cyano, trifluoromethyl, nitro, amino, â€”NH(C1-C4 alkyl), â€”N(C1-C2 alkyl)(C1-C6 alkyl), â€”C(&boxH;O)O(C1-C4 alkyl), â€”C(&boxH;O)(C1-C4 alkyl), â€”COOH, â€”SO2NH(C1-C4 alkyl), â€”SO2N(C1-C2 alkyl)(C1-C4 alkyl), â€”SO2NH2, â€”NHSO2(C1-C4 alkyl), â€”S(C1-C6 alkyl) and â€”SO2(C1-C6 alkyl), and wherein each of the C1-C4 alkyl and C1-C6 alkyl moieties in the foregoing R5 groups may optionally be substituted with one or two substituents independently selected from fluoro, hydroxy, amino, methylamino, dimethylamino and acetyl; R7 is hydrogen, methyl, halo (e.g., chloro, fluoro, iodo or bromo), hydroxy, methoxy, â€”C(&boxH;O)(C1-C2 alkyl), â€”C(&boxH;O)O(C1-C2 alkyl), trifluoromethoxy, hydroxymethyl, trifluoromethyl or formyl; R10 is hydrogen, hydroxy, methoxy or fluoro; R11 is hydrogen or C1-C4 alkyl; R12 is, hydrogen or methyl; and Z is NH, oxygen, sulfur, â€”N(C1-C4 alkyl), or CR13R14 wherein R13 and R14 are independently selected from hydrogen, and methyl with the exception that one of R13 and R14 may optionally be cyano; with the further proviso that: (a) in the six or seven membered rings of structures in formula I, there can not be two double bonds adjacent to each other; and (b) when D is carbon and is double bonded to B, then B is CR1R2; or a pharmaceutically acceptable salt thereof.