Aromatic heterocyclic derivatives as enzyme inhibitors

A compound of the formula:

• wherein
• (a) X is selected from the group consisting of —S(O)2—, —NH—S(O)2—, —N(R′)—S(O)2—, —C(═O)—, —OC(═O)—, —NH—C(═O)—, and a direct link, wherein R′ 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, —CF3, —CF2CF3, —CH(CF3)2, —COH(CF3)2, cyano, nitro, —C(O)OH, —C(O)OZ1, —Z1, —OZ1, —OH, —P(O)3H2, —P(O)3(Z1)2, tetrazolyl, —S(O)3H and —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 —C(O)OH, then Y2 is hydrogen, —OH or —C(O)OH;
• (3) when Y1 is —C(O)OZ1, then Y2 is hydrogen, —OH or —C(O)OZ1;
• (4) when Y1 is —Z1, then Y2 is hydrogen, —OH or —Z1;
• (5) when Y1 is —CF3, then Y2 is hydrogen, —OH or —CF3;
• (6) when Y1 is —OZ1, then Y2 is hydrogen, —OH or −OZ1;
• (7) when Y1 is —OH, then Y2 is hydrogen, —OH, —C(O)OH, —C(O)OZ1, —CF3, —S(O)3H, or —S(O)mZ1;
• and
• (8) when Y1 is cyano, nitro, —P(O)3H2, —P(O)3(Z1)2, or tetrazolyl, then Y2 is hydrogen;
• (c) R2 is selected from the group consisting of
• where W is nitrogen or carbon;
• and
• (d) Het is selected from the group consisting of
• wherein 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.