Patent ID: 6232299
Filing Date: 2001-05-15
Classification: A61K,A61P

Abstract:
A method for treating a neoplastic condition sensitive to the combination below which comprises administering to a mammal in need of such treatment an effective amount of an oncolytic agent having an anti-neoplastic effect in combination with a protein kinase C inhibitor selective for a beta-1 or beta-2 isozyme of protein kinase C, wherein the protein kinase C inhibitor is administered in an amount sufficient to enhance the anti-neoplastic effect of the oncolytic agent, and wherein the protein kinase C inhibitor is a bis-indolylmaleimide or a macrocyclic bis-indolylmaleimide and has the following formula: ##STR5##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.sup.3 --, --NOR.sup.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's are hydrogen or up to four optional substituents independently selected from halo, C.sub.1 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkoxy, haloalkyl, nitro, NR.sup.4 R.sup.5, or --NHCO(C.sub.1 -C.sub.4 alkyl);R.sup.2 is hydrogen, CH.sub.3 CO--, NH.sub.2, or hydroxy;R.sup.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.sup.4 R.sup.5, --(C.dbd.NH)NH.sub.2, --SO(C.sub.1 -C.sub.4 alkyl), --SO.sub.2 (NR.sup.4 R.sup.5), or --SO.sub.2 (C.sub.1 -C.sub.4 alkyl);R.sup.4 and R.sup.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; andn is independently 2, 3, 4, or 5, or a pharmaceutically acceptable salt, prodrug or ester thereof.