化学
部分
立体化学
IC50型
吡啶
激酶
结构-活动关系
铅化合物
选择性
体外
药物化学
生物化学
催化作用
作者
Huimin Liu,Yongli Duan,Hehua Xiong,Jianqing Zhang,Shunmin Huang,Ting Chen,Pengwu Zheng,Qidong Tang
标识
DOI:10.1016/j.bmcl.2019.126848
摘要
A series of pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety were designed, synthesized and evaluated for the anti-proliferative on three cancer cell lines (A549, HepG2 and MCF-7) in vitro. Most of the compounds showed moderate to high potency. Some excellent compounds were tested for the inhibitory activity of c-Met kinase. Compound 34 (c-Met IC50 = 17 nM) was investigated the selectivity against Flt-3, c-Kit, VEGFR-2, ALK, PDGFR-β and RON. Structure-activity relationship studies indicated that hydrogen, fluorine atom, and mono-electron-withdrawing groups (mono-EWGs, such as R2 = F) on R, R1 and R2, respectively, were beneficial for the anti-proliferative activities of the target compounds. Besides, we have took further study on the combined mode between compound 34 and c-Met kinase through molecular docking.
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