Discovery of N-(2-chloro-6-methylphenyl)-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
Discovery of N-(2-chloro-6-methylphenyl)-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
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DOI：
10.1021/jm049486a
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发表时间：
2004-12-30
影响因子：
7.3
通讯作者：
Borzilleri, RM
中科院分区：
文献类型：
--
作者：
Lombardo, LJ;Lee, FY;Borzilleri, RM
一系列取代的2-（氨基吡啶基）-和2-（氨基嘧啶基）噻唑-5-甲酰胺被鉴定为有效的Src/Abl激酶抑制剂，其对血液和实体瘤细胞系具有优异的抗增殖活性。化合物13在慢性骨髓性白血病（CML）的K562异种移植模型中具有口服活性，在多个剂量水平下显示出完全的肿瘤消退和低毒性。基于其稳健的体内活性和有利的药代动力学特征，选择13用于肿瘤适应症的额外表征。
A series of substituted 2-(aminopyridyl)- and 2-(aminopyrimidinyl)thiazole-5-carboxamides was identified as potent Src/Abl kinase inhibitors with excellent anti proliferative 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.