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.

中文翻译：

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3-（2,6-二氯-3,5-二甲氧基-苯基）-1- {6- [4-（4-乙基-哌嗪-1-基）-苯基氨基]-嘧啶-4-基}-的发现1-甲基脲（NVP-BGJ398），受体酪氨酸激酶的成纤维细胞生长因子受体家族的有效和选择性抑制剂。

通过合理设计芳基环的取代方式，已优化了一系列新的N-芳基-N'-嘧啶-4-基尿素，以提供有效和选择性的成纤维细胞生长因子受体酪氨酸激酶1、2和3抑制剂。 。根据其体外概况，选择化合物1h（NVP-BGJ398）进行体内评估，并在过表达野生型FGFR3的RT112膀胱癌异种移植模型中显示出显着的抗肿瘤活性。这些结果支持1h作为新的抗癌药的潜在治疗用途。