Fibroblast growth factor receptor 3 (FGFR3) is an attractive therapeutic target for the treatment of bladder cancer. We identified 1,3,5-triazine derivative 18b and pyrimidine derivative 40a as novel structures with potent and highly selective FGFR3 inhibitory activity over vascular endothelial growth factor receptor 2 (VEGFR2) using a structure-based drug design (SBDD) approach. X-ray crystal structure analysis suggests that interactions between 18b and amino acid residues located in the solvent region (Lys476 and Met488), and between 40a and Met529 located in the back pocket of FGFR3 may underlie the potent FGFR3 inhibitory activity and high kinase selectivity over VEGFR2.

中文翻译：

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1,3,5-三嗪和嘧啶衍生物作为新型FGFR3抑制剂的结构设计药物设计，对VEGFR2具有高选择性。

成纤维细胞生长因子受体3（FGFR3）是治疗膀胱癌的有吸引力的治疗靶标。我们使用基于结构的药物设计（SBDD）方法，将1,3,5-三嗪衍生物18b和嘧啶衍生物40a确定为对血管内皮生长因子受体2（VEGFR2）具有有效且高度选择性的FGFR3抑制活性的新型结构。X射线晶体结构分析表明，18b与位于溶剂区域（Lys476和Met488）以及位于FGFR3后袋的40a和Met529之间的氨基酸残基之间的相互作用可能是强FGFR3抑制活性和高激酶选择性的基础。 VEGFR2。