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

页码：2408 / 2413

页数：6

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