Patent ID: 6040313
Filing Date: 2000-03-21
Classification: A61P,C07D

Abstract:
A method of treating leukemia or solid tumors susceptible to CPT in a mammal in need thereof, comprising administering to said mammal an effective amount for treating said leukemia or said solid tumors susceptible to CPT, a camptothecin ester having the structure: ##STR5## wherein R.sup.6 is cyano, formyl, hydroxy, C.sub.1-8 alkoxy, nitro, amino, halogen, trifluoromethyl, aminomethyl, azido, amido, hydrazino, OC(O)R.sup.7 or OC(O)NR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 are, independently hydrogen or C.sub.1-8 alkyl; andZ.sup.1 is H, C.sub.1-8 alkyl, CH.sub.2 NR.sup.1 R.sup.2 where (a) R.sup.1 and R.sup.2 are, independently, hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-C.sub.1-6 alkyl, C.sub.2-6 alkenyl, hydroxy-C.sub.1-6 alkyl, C.sub.1-6 alkoxy-C.sub.1-6 alkyl, (b) R.sup.1 is hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-C.sub.1-6 alkyl C.sub.2-6 alkenyl, hydroxy-C.sub.1-6 alkyl or C.sub.1-6 alkoxy-C.sub.1-6 alkyl and R.sup.2 is --COR.sup.3 where R.sup.3 is hydrogen, C.sub.1-6 alkyl, perhalo-C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-C.sub.1-6 alkyl, C.sub.2-6 alkenyl, hydroxy-C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy-C.sub.1-6 alkyl, or (c) R.sup.1 and R.sup.2 taken together with the nitrogen atom to which they are attached form a saturated 3-7 membered heterocyclic ring which may contain a O, S or NR.sup.4 group, where R.sup.4 is hydrogen, C.sub.1-6 alkyl, perhalo-C.sub.1-6 alkyl, aryl, aryl substituted with one or more groups selected from the group consisting of C.sub.1-6 alkyl, halogen, nitro, amino, C.sub.1-6 alkylamino, perhalo-C.sub.1-6 alkyl, hydroxy-C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy-C.sub.1-6 alkyl and --COR.sup.5 where R.sup.5 is hydrogen, C.sub.1-6 alkyl, perhalo-C.sub.1-6 alkyl, C.sub.1-6 alkoxy, aryl, and aryl substituted with one or more C.sub.1-6 alkyl, perhalo-C.sub.1-6 alkyl, hydroxy-C.sub.1-6 alkyl, or C.sub.1-6 alkoxy-C.sub.1-6 alkyl groups;R.sup.9 is the side chain of one or the naturally occurring .alpha.-amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, proline, phenylalanine, tyrosine, tryptophan, lysine, arginine, histidine, aspartate, glutamate, asparagine, glutamine, cysteine and methionine;R.sup.10 and R.sup.11 are, independently, hydrogen or C.sub.1-8 alkyl;m is an integer of 1 to 6; andn is an integer of 1 or 2; and pharmaceutically acceptable salts thereof.