Protein kinase C inhibitors

A method of inhibiting protein kinase C beta-1 isozyme, which comprises administering to a mammal in need of such treatment a pharmaceutically effective amount of a compound of the formula:

• ##STR74## wherein;
• W is --O--, --S--, --SO--, --SO.sub.2 --, --CO--, C.sub.2 -C.sub.6 alkylene, substituted alkylene, C.sub.2 -C.sub.6 alkenylene, -aryl-, -aryl(CH.sub.2).sub.m O- -heterocycle-, -heterocycle-(CH.sub.2).sub.m O-, -fused bicyclic-, -fused bicyclic-(CH.sub.2).sub.m O-, --NR.sub.3 --, --NOR.sub.3 --, --CONH--, or --NHCO--;
• X and Y are independently C.sub.1 -C.sub.4 alkylene, substituted alkylene, or together X, Y, and W combine to form --(CH.sub.2).sub.n -AA-;
• R.sub.1 is independently hydrogen, halo, C.sub.1 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkoxy, haloalkyl, nitro, NR.sub.4 R.sub.5, or --NHCO(C.sub.1 -C.sub.4 alkyl);
• R.sub.2 is hydrogen, CH.sub.3 CO--, NH.sub.2, or hydroxy;
• R.sub.3 is hydrogen, (CH.sub.2).sub.m aryl, C.sub.1 -C.sub.4 alkyl, --COO(C.sub.1 -C.sub.4 alkyl), --CONR.sub.4 R.sub.5, --(C.dbd.NH)NH.sub.2, --SO(C.sub.1 -C.sub.4 alkyl), --SO.sub.2 (NR.sub.4 R.sub.5), or --SO.sub.2 (C.sub.1 -C.sub.4 alkyl);
• R.sub.4 and R.sub.5 are independently hydrogen, C.sub.1 -C.sub.4 alkyl, phenyl, benzyl, or combine to the nitrogen to which they are bonded to form a saturated or unsaturated 5 or 6 member ring;
• AA is an amino acid residue;
• m is independently 0, 1, 2, or 3;
• and
• n is independently 2, 3, 4, or 5;
• or
• a pharmaceutically acceptable salt or solvate thereof.

A method of inhibiting protein kinase C beta-2 isozyme, which comprises administering to a mammal in need of such treatment a pharmaceutically effective amount of a compound of the formula:

• ##STR75## wherein:
• W is --O--, --S--, --SO--, --SO.sub.2 --, --CO--, C.sub.2 -C.sub.6 alkylene, substituted alkylene, C.sub.2 -C.sub.6 alkenylene, -aryl-, -aryl(CH.sub.2).sub.m O- -heterocycle-, heterocycle-(CH.sub.2).sub.m O-, -fused bicyclic-, -fused bicyclic-(CH.sub.2).sub.m O-, --NR.sub.3 --, --NOR.sub.3 --, --CONH--, or --NHCO--;
• X and Y are independently C.sub.1 -C.sub.4 alkylene, substituted alkylene, or together X, Y, and W combine to form --(CH.sub.2).sub.n -AA-;
• R.sub.1 is independently hydrogen, halo, C.sub.1 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkoxy, haloalkyl, nitro, NR.sub.4 R.sub.5, or --NHCO(C.sub.1 -C.sub.4 alkyl);
• R.sub.2 is hydrogen, CH.sub.3 CO--, NH.sub.2, or hydroxy;
• R.sub.3 is hydrogen, (CH.sub.2).sub.m aryl, C.sub.1 -C.sub.4 alkyl, --COO(C.sub.1 -C.sub.4 alkyl), --CONR.sub.4 R.sub.5, --(C.dbd.NH)NH.sub.2, --SO(C.sub.1 -C.sub.4 alkyl), --SO.sub.2 (NR.sub.4 R.sub.5), or --SO.sub.2 (C.sub.1 -C.sub.4 alkyl);
• R.sub.4 and R.sub.5 are independently hydrogen, C.sub.1 -C.sub.4 alkyl, phenyl, benzyl, or combine to the nitrogen to which they are bonded to form a saturated or saturated or unsaturated 5or 6 member ring;
• AA is an amino acid residue;
• m is independently 0, 1, 2, or 3;
• and
• n is independently 2, 3, 4, or 5;
• or
• a pharmaceutically acceptable salt or solvate thereof.