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 and solid tumor cell lines. Compound 13 was orally active in a K562 xenograft model of chronic myelogenous leukemia (CML), demonstrating complete tumor regressions and low toxicity at multiple dose levels. On the basis of its robust in vivo activity and favorable pharmacokinetic profile, 13 was selected for additional characterization for oncology indications.

中文翻译：

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N-（2-氯-6-甲基-苯基）-2-（6-（4-（2-羟乙基）-哌嗪-1-基）-2-甲基嘧啶-4-基氨基）噻唑-5-羧酰胺的发现（BMS-354825），一种在临床前测定中具有有效抗肿瘤活性的双重Src / Abl激酶抑制剂。

一系列取代的2-（氨基吡啶基）-和2-（氨基嘧啶基）噻唑-5-羧酰胺被确定为有效的Src / Abl激酶抑制剂，对血液和实体瘤细胞系具有优异的抗增殖活性。化合物13在慢性粒细胞白血病（CML）的K562异种移植模型中具有口服活性，证明在多个剂量水平下肿瘤完全消退且毒性低。基于其强大的体内活性和良好的药代动力学特征，选择了13种药物用于肿瘤适应症的其他表征。