3-amino-2-oxo-1-piperidineacetic derivatives as enzyme inhibitors

A compound of the formula:

• ##STR94## wherein (a) X is selected from the group consisting of --S(O).sub.2 --, --N(R')--S(O).sub.2 --, --(C.dbd.O)--, --OC(.dbd.O)--, --NH--C(.dbd.O)--, --P(O)(R")-- and a direct link, wherein R' is hydrogen, alkyl of 1 to about 4 carbon atoms, aryl of about 6 to about 14 carbon atoms or aralkyl of about 6 to about 16 carbon atoms, and R" is NR', OR', R', or SR', with the proviso that R" is not NH, OH, H, or SH, and;
• (b) R.sub.1 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, which optionally is substituted in the ring carbons with hydroxyl, amino, guanidino, amidino, or alkoxyl or alkyl each of which having 1 to about 3 carbons,
• (3) cyclic alkyl of 3 to about 15 carbon atoms, which optionally is substituted in the ring carbons with hydroxyl, amino, guanidino, amidino, or alkoxyl or alkyl each of which having 1 to about 3 carbons,
• (4) heterocycloalkyl of 4 to about 10 ring atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from the group consisting of oxygen, nitrogen, and S(O).sub.i, wherein i is 0, 1, or 2, optionally substituted in the ring carbons with hydroxyl, alkoxyl or alkyl each of which having 1 to about 3 carbons, amino, guanidino, or amidino,
• (5) heterocyclo of 4 to about 10 ring atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from the group consisting of oxygen, nitrogen, and S(O).sub.i, wherein i is 0, 1, or 2, optionally substituted in the ring carbons with hydroxyl, alkoxyl or alkyl each of which having 1 to about 3 carbons, amino, guanidino, or amidino,
• (6) alkenyl of about 3 to about 6 carbon atoms which is optionally substituted with cyclic alkyl of about 5 to about 8 carbon atoms, which optionally is substituted in the ring carbons with hydroxyl, amino, guanidino, amidino, or alkoxyl or alkyl each of which having 1 to abut 3 carbons,
• (7) aryl of about 6 to about 14 carbon atoms which is optionally mono-, di- or tri-substituted with Y.sub.1, Y.sub.2, and/or Y.sub.3, respectively,
• (8) heteroaryl of 5 to 14 atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from oxygen, nitrogen, and S(O).sub.i, wherein i is 0, 1, or 2, optionally mono-, di- or tri-substituted with Y.sub.1, Y.sub.2, and/or Y.sub.3, respectively,
• (9) aralkyl of about 7 to about 15 carbon atoms which is optionally mono-, di-, or tri-substituted in the aryl ring with Y.sub.1, Y.sub.2, and/or Y.sub.3, respectively,
• (10) heteroaralkyl of 6 to 11 atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from oxygen, nitrogen, and S(O).sub.i, wherein i is 0, 1, or 2, optionally mono-, di- or tri-substituted with Y.sub.1, Y.sub.2, and/or Y.sub.3, respectively,
• (11) aralkenyl of about 8 to about 15 carbon atoms which is optionally mono-, di-, or tri-substituted in the aryl ring with Y.sub.1, Y.sub.2, and/or Y.sub.3, respectively,
• (12) heteroaralkenyl of 7 to 12 atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from oxygen, nitrogen, and S(O).sub.i, wherein i is 0, 1, or 2, optionally mono-, di- or tri-substituted with Y.sub.1, Y.sub.2, and/or Y.sub.3, respectively, ##STR95## (17) perfluoroalkyl of 1 to about 12 carbon atoms, (18) perfluoroaryl of about 6 to about 14 carbon atoms,
• (19) perfluoroaralkyl of about 7 to about 15 carbon atoms,
• (20) hydrogen, and
• (21) ##STR96## is a 5 to 7 member heterocycle of 3 to 6 ring carbon atoms, where V is --CH.sub.2 --, --O--, --S(.dbd.O)--, --S(O).sub.2 -- or --S--, wherein Y.sub.1, Y.sub.2, and Y.sub.3 are
• (i) independently selected from the group consisting of hydrogen, halogen, cyano, tetrazolyl, amino, guanidino, amidino, methylamino, and methylguanidino, --CF.sub.3, --CF.sub.2 H, --CF.sub.2 CF.sub.3, --CH(CF.sub.3).sub.2, --C(OH)(CF.sub.3).sub.2, OCF.sub.3, OCF.sub.2 CF.sub.3, --OC(O)NH.sub.2, --OC(O)NHZ.sub.1, --OC(O)NZ.sub.1 Z.sub.2, --NHC(O)Z.sub.1, --NHC(O)NH.sub.2, --NHC(O)NZ.sub.1, --NHC(O)NZ.sub.1 Z.sub.2, --C(O)OH, --C(O)NH.sub.2, --C(O)NHZ.sub.1, --C(O)OZ.sub.1, --P(O).sub.3 H, --P(O).sub.3 H.sub.2, --P(O).sub.3 (Z.sub.1).sub.2, --S(O).sub.3 H, --S(O).sub.m Z.sub.1, --Z.sub.1, --OZ.sub.1, --OH, --NH.sub.2, --NHZ.sub.1, and --NZ.sub.1 Z.sub.2, wherein m is 0, 1 or 2, and Z.sub.1 and Z.sub.2 are independently selected from the group consisting of alkyl of 1 to about 12 carbon atoms, aryl of about 6 to about 14 carbon atoms, heteroaryl of about 5 to about 14 atoms having 1 to about 9 carbon atoms, aralkyl of about 7 to about 15 carbon atoms, and heteroaralkyl of about 6 to about 11 atoms having about 3 to about 9 carbon atoms, or
• (ii) Y.sub.1 and Y.sub.2 are selected together to be --OC(Z.sub.3)(Z.sub.4)O, wherein Z.sub.3 and Z.sub.4 are independently selected from the group consisting of hydrogen, alkyl of 1 to about 12 carbon atoms, aryl of about 6 to about 14 carbon atoms heteroaryl of about 5 to about 14 atoms having 1 to about 9 carbon atoms, aralkyl of about 7 to about 15 carbon atoms, and heteroaralkyl of about 6 to about 11 atoms having about 3 to about 9 carbon atoms,
• (c) Q is --(CH.sub.2).sub.n --, wherein n is an integer from 1 to 4, or --(CH.sub.2).sub.q R.sub.4 --, wherein q is 1 or 2, and R.sub.4 is --S(O).sub.p --, --O--, --N(R.sub.5)--, wherein p is 0, 1, or 2 and R.sub.5 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, and aryl of 1 to 4 carbon atoms;
• (d) R.sub.2 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 4 carbon atoms;
• and
• (e) Y is selected from the group of R.sub.1 substituents, with the proviso that Y is not ##STR97## and pharmaceutically acceptable salts thereof.