Novel 5-(benzyloxy)pyridin-2(1H)-one derivatives as potent c-Met inhibitors

被引：7
|
作者：
Zhang, Dengyou [1 ]
Ai, Jing [2 ]
Liang, Zhongjie [3 ]
Zhu, Wei [1 ]
Peng, Xia [2 ]
Chen, Xianjie [1 ]
Ji, YinChun [2 ]
Jiang, Hualiang [1 ,4 ]
Luo, Cheng [1 ]
Geng, Meiyu [2 ]
Liu, Hong [1 ]
机构：
[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
[3] Soochow Univ, Ctr Syst Biol, Suzhou 215006, Jiangsu, Peoples R China
[4] E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 08期
基金：
中国国家自然科学基金;
关键词：
c-Met; EBC-1; cell; Tyrosine kinase receptor; KINASE INHIBITORS; DISCOVERY;
D O I：
10.1016/j.bmcl.2013.02.037
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of novel 5-(benzyloxy)pyridin-2(1H)-ones were designed, synthesized and biologically evaluated for c-Met inhibition. Various amides and benzoimidazoles at C-3 position were investigated. A potent compound 12b with a c-Met IC50 of 12 nM was identified. This compound exhibited potent inhibition of EBC-1 cell associated with c-Met constitutive activation and showed high selectivity for c-Met than other tested 11 kinases. The binding model 12b with c-Met was disclosed by docking analysis. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2408 / 2413
页数：6
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