Patent ID: 6608204
Filing Date: 2003-08-19
Classification: A61K,C07D,C07K

Abstract:
A compound of the formula: wherein(a) X is selected from the group consisting of â€”S(O)2â€”, â€”NHâ€”S(O)2â€”, â€”N(Râ€²)â€”S(O)2â€”, â€”C(&boxH;O)â€”, â€”OC(&boxH;O)â€”, â€”NHâ€”C(&boxH;O)â€”, and a direct link, wherein Râ€² is alkyl of 1 to about 4 carbon atoms; (b) R1 is selected from the group consisting of: (1) alkyl of 1 to about 12 carbon atoms, (2) alkyl of 1 to about 3 carbon atoms substituted with cyclic alkyl of about 5 to about 8 carbon atoms, (3) alkenyl of about 3 to about 6 carbon atoms which is optionally substituted with cyclic alkyl of about 5 to about 8 carbon atoms, (4) aryl of about 4 to about 14 carbon atoms which is optionally mono-substituted with yl or optionally di-substituted with Y1 and Y2, (5) aralkyl of about 5 to about 15 carbon atoms which is optionally mono-substituted in the aryl ring with Y1 or optionally di-substituted in the aryl ring with Y1 and Y2, (6) aralkenyl of about 6 to about 15 carbon atoms which is optionally mono-substituted in the aryl ring with Y1 or optionally di-substituted in the aryl ring with Y1 and Y2, (11) perfluoroalkyl of 1 to about 12 carbon atoms, (12) perfluoroaryl of about 6 to about 14 carbon atoms, (13) perfluoroaryl alkyl of about 7 to about 15 carbon atoms, and (14) hydrogen, where Y1 and Y2 are independently selected from halogen, â€”CF3, â€”CF2CF3, â€”CH(CF3)2, â€”COH(CF3)2, cyano, nitro, â€”C(O)OH, â€”C(O)OZ1, â€”Z1, â€”OZ1, â€”OH, â€”P(O)3H2, â€”P(O)3(Z1)2, tetrazolyl, â€”S(O)3H and â€”S(O)mZ1 wherein m is 0, 1 or 2, Z1 is alkyl of 1 to about 12 carbon atoms, aryl of about 4 to about 14 carbon atoms and aralkyl of about 5 to about 15 carbon atoms, with the provisos that: (1) when Y1 is halogen, then Y2 is hydrogen or halogen; (2) when Y1 is â€”C(O)OH, then Y2 is hydrogen, â€”OH or â€”C(O)OH; (3) when Y1 is â€”C(O)OZ1, then Y2 is hydrogen, â€”OH or â€”C(O)OZ1; (4) when Y1 is â€”Z1, then Y2 is hydrogen, â€”OH or â€”Z1; (5) when Y1 is â€”CF3, then Y2 is hydrogen, â€”OH or â€”CF3; (6) when Y1 is â€”OZ1, then Y2 is hydrogen, â€”OH or âˆ’OZ1; (7) when Y1 is â€”OH, then Y2 is hydrogen, â€”OH, â€”C(O)OH, â€”C(O)OZ1, â€”CF3, â€”S(O)3H, or â€”S(O)mZ1; and (8) when Y1 is cyano, nitro, â€”P(O)3H2, â€”P(O)3(Z1)2, or tetrazolyl, then Y2 is hydrogen; (c) R2 is selected from the group consisting of â€ƒwhere W is nitrogen or carbon; and (d) Het is selected from the group consisting of â€ƒwherein R3 is hydrogen, alkyl of 1 to about 2 carbon atoms, or cycloalkyl of about 3 carbon atoms, R4 is hydrogen or methyl, and pharmaceutically acceptable salts thereof, with the proviso that when X is other than a direct link R1 is not hydrogen.