Preparation of 2-cyano-acrylamide compounds as protein kinase inhibitors.

Abstract

Disclosed are compds. I [A = -NH- or -O-; B1, B2 = independently H, halo or alkyl; B1 and B2 may combine to form S-contg. unsatd. 5-membered heterocycle; X = aryl or heteroaryl; Y = alkyl or heterocycloalkyl (optionally substituted with alkyl); R1, R2 = independently H or alkyl; or pharmaceutically acceptable salts thereof]. For example, compd. II was prepd. from 3-nitrobenzaldehyde via condensation reaction with 2-cyano-N,N-dimethylacetamide, redn., treatment with 2,4,5-trichloropyrimidine/K2CO3, and Pd2(dba)3-catalyzed rection with 4-(4-methyl-1-piperazinyl)aniline. In protein kinase inhibition assay, the exemplified compd. II showed 11%, 93%, 92%, and 87% inhibition at 1 μM for EGFR WT, EGFR T790M, BTK, and JAK3, resp. Compds. I are claimed useful for the treatment of solid tumor, hematol. or blood tumor, inflammatory disease and immunol. disease. [on SciFinder(R)]