Patent ID: 6362188
Filing Date: 2002-03-26
Classification: A61P,C07D

Abstract:
A compound of the formula: or a pharmaceutically acceptable salt or solvate thereof, whereinone of a, b, c and d represents N or N+Oâˆ’, and the remaining a, b, c and d groups represent CR1 or CR2; each R1 and each R2 is independently selected from H, halo, â€”CF3, â€”OR10, â€”COR10, â€”SR10, â€”S(O)tR11 (wherein t is 0, 1 or 2), â€”N(R10)2, â€”OC(O)R10, â€”CO2R10, â€”OCO2R11, â€”CN, â€”NR10COOR11, â€”SR11C(C(O)OR11, â€”SR11N(R75)2 (provided that R11 in â€”SR11N(R75)2 is not â€”CH2â€”) wherein each R75 is independently selected from H, â€”C(O)OR11, benzotriazol-1-yloxy, tetrazol-5-ylthio, substituted tetrazol-5-ylthio, alkynyl, alkenyl or alkyl, said alkyl or alkenyl group optionally being substituted with halo, â€”OR10 or â€”CO2R10; R3 and R4 are the same or different and each independently represents H, any of the substituents of R1 and R2, or R3 and R4 taken together represent a saturated or unsaturated C5-C7 fused ring to the benzene ring (Ring III); R5, R6, and R7 each independently represents H, â€”CF3, â€”COR10, alkyl or aryl, said alkyl or aryl optionally being substituted with â€”OR10, â€”SR10, â€”S(O)tR11, â€”NR10COOR11, â€”N(R10)2, â€”NO2, â€”COR10, â€”OCOR10, â€”OCO2R11, â€”CO2R10, OPO3R10, or R5 is combined with R6 to represent &boxH;O or &boxH;S; provided that for the groups â€”OR10, â€”SR10, and â€”N(R10)2R10 is not H; R10 represents H, alkyl, aryl, or aralkyl; R11 represents alkyl or aryl; X represents N and the optional bond (represented by the dotted line) to carbon atom 11 is absent; the dotted line between carbon atoms 5 and 6 represents an optional bond, such that when a double bond is present, A and B independently represent â€”R10, halo, â€”OR11, â€”OCO2R11 or â€”OC(O)R10, and when no double bond is present between carbon atoms 5 and 6, A and B each independently represent H2, â€”(OR11)2, H and halo, dihalo, alkyl and H, (alkyl)2, â€”H and â€”OC(O)R10, H and â€”OR10, &boxH;O, aryl and H, &boxH;NOR10 or â€”Oâ€”(CH2)pâ€”Oâ€” wherein p is 2, 3 or 4; R8 represents a heterocyclic ring selected from: â€ƒsaid heterocyclic rings (2.0 to 7.0 and 2.1 to 7.1) being optionally substituted with one or more substituents independently selected from: (a) alkyl, (b) substituted alkyl wherein said substituents are selected from: halo, aryl, â€”OR15, â€”N(R15)2, heteroaryl, heterocycloalkyl, or cycloalkyl, wherein each R15 group is the same or different, provided that said optional substituent is not bound to a carbon atom that is adjacent to an oxygen or nitrogen atom, and wherein R15 is selected from: H, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or cycloalkylalkyl; (c) hydroxyl, with the proviso that carbon atoms adjacent to the nitrogen, sulfur or oxygen atoms of the ring are not substituted with hydroxyl; (d) alkyloxy; or (e) arylalkyloxy; Y represents CH2, NR16, O, S, SO, or SO2 wherein R16 is selected from: H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, acyl, aroyl, carbamoyl, carboxamido, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, sulfonamido, alkylsulfonamido, arylsulfonamido or arylalkylsulfonamido; n is 0 to 6; Q represents O or N, provided that Q is not adjacent to a heteroatom in the heterocycloalkyl rings of 2.1, 3.1, 4.1, 5.1, 6.1 and 7.1; R12 is selected from: â€ƒwherein R17 is selected from: (1) H, (2) alkyl, (3) aryl, (4) arylalkyl, (5) substituted arylalkyl wherein the substituents are selected from halo or CN, (6) â€”C(aryl)3, (7) cycloalkyl, (8) substituted alkyl (as defined above in (b)), or (9) cycloalkylalkyl; R12A is selected from rings 8.0 or 9.1, defined above; said imidazolyl ring 8.0 optionally being substituted with one or two substituents, said imidazole ring 9.0 optionally being substituted with 1-3 substituents, and said pyridyl ring 9.1 optionally being substituted with 1-4 substituents, wherein said optional substituents for rings 8.0, 9.0 and 9.1 are bound to the carbon atoms of said rings and are independently selected from: â€”NHC(O)R15, â€”C(R16)2OR19, â€”OR15, â€”SR15, F, Cl, Br, alkyl, substituted alkyl (as defined above in (b)), aryl, arylalkyl, cycloalkyl, or â€”N(R15)2; R15 is as defined above; each R18 is independently selected from H or alkyl; R19 is selected from H or â€”C(O)NHR20, and R20 is as defined below; R13 and R14 for each n are independently selected from: H, F, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl or â€”CON(R15)2 (wherein R15 is as defined above), â€”OR15 or â€”N(R15)2 provided that the â€”OR15 and â€”N(R15)2 groups are not bound to a carbon atom that is adjacent to a nitrogen atom, and provided that there can be only one â€”OH group on each carbon; and the substitutable R13 and R14 groups are optionally substituted with one or more substituents selected from: F, alkyl, cycloalkyl, arylalkyl, or heteroarylalkyl; or R13 and R14, for each n, together with the carbon atom to which they are bound, form a C3 to C6 cycloalkyl ring; R9 is selected from: R20 is selected from: H, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, or heterocyloalkylalkyl, provided that R20 is not H when R9 is group 12.0 or 16.0; when R20 is other than H, then said R20 group is optionally substituted with one or more substituents selected from, halo, alkyl, aryl, â€”OC(O)R15, â€”OR15 or â€”N(R15)2, wherein each R15 group is the same or different, and wherein R15 is as defined above, provided that said optional substituent is not bound to a carbon atom that is adjacent to an oxygen or nitrogen atom; R21 is selected from: H, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; R21 is other than H, then said R21 group is optionally substituted with one or more substituents selected from: alkyl, or aryl; and R22 is selected from cycloalkyl, heterocycloalkyl, aryl, substituted aryl, alkyl, substituted alkyl or substituted cycloalkyl.