Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors,RSC Advances

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Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as potent fibroblast growth factor receptor inhibitors
RSC Advances ( IF 3.9 ) Pub Date : 2021-6-9 , DOI: 10.1039/d1ra02660g
Xingping Su ₁ , Zhihao Liu ₁ , Lin Yue ₁ , Xiuli Wu ₁ , Wei Wei ₁ , Hanyun Que ₁ , Tinghong Ye ₁ , Yi Luo ₂ , Yiwen Zhang ₁

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Abnormal activation of FGFR signaling pathway plays an essential role in various types of tumors. Therefore, targeting FGFRs represents an attractive strategy for cancer therapy. Herein, we report a series of 1H-pyrrolo[2,3-b]pyridine derivatives with potent activities against FGFR1, 2, and 3. Among them, compound 4h exhibited potent FGFR inhibitory activity (FGFR1–4 IC₅₀ values of 7, 9, 25 and 712 nM, respectively). In vitro, 4h inhibited breast cancer 4T1 cell proliferation and induced its apoptosis. In addition, 4h also significantly inhibited the migration and invasion of 4T1 cells. Furthermore, 4h with low molecular weight would be an appealing lead compound which was beneficial to the subsequent optimization. In general, this research has been developing a class of 1H-pyrrolo[2,3-b]pyridine derivatives targeting FGFR with development prospects.

中文翻译：

1H-吡咯并[2,3-b]吡啶衍生物作为有效的成纤维细胞生长因子受体抑制剂的设计、合成和生物学评价

FGFR信号通路的异常激活在各种类型的肿瘤中起着至关重要的作用。因此，靶向 FGFRs 代表了一种有吸引力的癌症治疗策略。在此，我们报道了一系列 1 H-吡咯并[2,3- b ] 吡啶衍生物，它们对 FGFR1、2 和 3 具有强效活性。其中，化合物4h表现出强效 FGFR 抑制活性（FGFR1-4 IC ₅₀值为 7 , 9, 25 和 712 nM, 分别)。在体外，4h抑制乳腺癌4T1细胞增殖并诱导其凋亡。此外，4h还显着抑制了4T1细胞的迁移和侵袭。此外，4h低分子量的先导化合物将是一种吸引人的先导化合物，有利于后续的优化。总的来说，本研究一直在开发一类靶向FGFR的1 H-吡咯并[2,3- b ]吡啶衍生物，具有发展前景。

更新日期：2021-06-09

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