Naphthyridinone compositions and methods for modulating c-kit and PDGFR receptors and their preparation.

Abstract

The invention provides compds. of formula I and pharmaceutical compns. thereof, which are useful as protein kinase inhibitors, as well as methods for using such compds. to treat, ameliorate or prevent a condition assocd. with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compds. to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit, PDGFR , PDGFR , CSF1R, Abl, BCR-Abl, CSK, JNK1, JNK2, p38, p70S6K, TGF , SRC, EGFR, trkB, FGFR3, FLT3, Fes, Lck, Syk, RAF, MKK4, MKK6, SAPK2 , BRK, KDR, c-raf or b-raf kinase, or mutant forms thereof. Compds. of formula I wherein Y and Z are independently CR and N; L is NRCO, CONR, CONRCONR, etc.; R1 and R3 are independently halo, (CR2)0-6-OH and derivs. (CR2)0-6-NH2 and derivs., (CR2)0-6-SH and derivs., etc.; R4 is (CR2)0-6-OH and derivs., (un)substituted C1-6 alkyl, (un)substituted C2-6 alkenyl, (un)substituted C2-6 alkynyl, etc.; R is H, C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, etc.; n is 0 - 2; and their pharamceutically acceptable salts thereof, are claimed. Example compd. II was prepd. by amidation of 3(5-amino-2-methylphenyl)-7-chloro-1-methyl-1H-[1,6]naphthyridin-2-one with 3-trifluoromethylbenzoyl chloride. All the invention compds. were evaluated for their kinase inhibitory activity (some data given). [on SciFinder(R)]