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Design, synthesis and molecular docking studies of some novel spiro[indoline-3, 4′-piperidine]-2-ones as potential c-Met inhibitors

Journal 2012 · IF 3.346 · 发表于 2012 年 2 月 18 日
作者: Lianbao Ye,Yuanxin Tian,Zhonghuang Li,Hong Jin,Zhengguang Zhu,Shanhe Wan,Junyan Zhang,Pengjiu Yu,Jiajie Zhang,Shuguang Wu
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摘要

Deregulation of receptor tyrosine kinase c-Met has been reported in human cancers and is considered as an attractive target for small molecule drug discovery . In this study, a series of spiro[indoline-3, 4′-piperidine]-2-ones were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibitory effect on c-Met with IC 50 values of 0.0147–17 μM in TR-FRET-based assay and IC 50 values of 1.56–1400 μM in cell-based assay. Furthermore, our docking experiments verified the results and explained the molecular mechanism of eminent activities to c-Met.

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