Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase
Discovery of 3-(2,6-Dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), A Potent and Selective Inhibitor of the Fibroblast Growth Factor Receptor Family of Receptor Tyrosine Kinase
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DOI：
10.1021/jm2006222
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发表时间：
2011-10-27
影响因子：
7.3
通讯作者：
Porta, Diana Graus
中科院分区：
文献类型：
--
作者：
Guagnano, Vito;Furet, Pascal;Porta, Diana Graus
通过合理设计芳环的取代模式，优化了一系列新的N-芳基-N'-嘧啶-4-基脲，以提供成纤维细胞生长因子受体酪氨酸激酶1、2和3的有效和选择性抑制剂。基于其体外特征，选择化合物Ih（NVP-BGJ398）用于体内评价，并且在过表达野生型FGFR 3的RT112膀胱癌异种移植物模型中显示出显著的抗肿瘤活性。这些结果支持了1h作为一种新的抗癌剂的潜在治疗用途。
A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the basis of its in vitro profile, compound 1h (NVP-BGJ398) was selected for in vivo evaluation and showed significant antitumor activity in RT112 bladder cancer xenografts models overexpressing wild-type FGFR3. These results support the potential therapeutic use of 1h as a new anticancer agent.