Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays.

摘要: A series of substituted 2-(aminopyridyl)- and 2-(aminopyrimidinyl)thiazole-5-carboxamides was identified as potent Src/Abl kinase inhibitors with excellent antiproliferative activity against hematological solid tumor cell lines. Compound 13 orally active in a K562 xenograft model chronic myelogenous leukemia (CML), demonstrating complete regressions low toxicity at multiple dose levels. On the basis its robust vivo favorable pharmacokinetic profile, selected for additional characterization oncology indications.