Preparation of novel aminoazaheterocyclic carboxamides useful in the treatment of hyperproliferative diseases.

Abstract

The invention provides substituted aminoazaheterocyclic carboxamide compds. according to formula I, their manuf. and use for the treatment of hyperproliferative diseases, such as cancer. Compds. of formula I wherein X is N and CR3; Y is NH, O and absent; R1 is L1R4L2R5L3L6, L1R4L2R5, L1R4; R2' and R2'' are independently H, halo, OH and derivs., SH and derivs., etc.; L1 and L3 are independently single bond and (un)substituted (un)branched C1-5 alkylene; R3 is H, halo, OH, CO2H, etc.; R4, R5 and R6 are independently aryl, heteroaryl, (un)substituted 3- to 7-membered monocyclic ring, etc.; L2 is NHCO, NHCO2, NHCONH, etc.; and pharmaceutically acceptable salts, solvates and prodrugs thereof, are claimed. Example compd. II was prepd. by methylation of 4-oxo-3,4-dihydroquinazoline-8-carboxylic acid; the resulting 4-oxo-3,4-dihydroquinazoline-8-carboxylic acid Me ester underwent chlorination and amination with 3-trifluoromethylbenzylamine to give 4-[(3-trifluoromethylbenzyl)amino]quinazoline-8-carboxylic acid Me ester, which underwent hydrolysis to give 4-[(3-trifluoromethylbenzyl)amino]quinazoline-8-carboxylic acid, which underwent amidation with ammonium chloride to give compd. II. All the invention compds. were evaluated for their hyperproliferative activity (data given). [on SciFinder(R)]