Discovery of Novel c-Met Inhibitors Bearing a 3-Carboxyl Piperidin-2-one Scaffold

Molecules

Wei Zhang³  Jing Ai¹  Dakuo Shi²  Xia Peng¹  Yinchun Ji¹  Jian Liu³  Meiyu Geng¹ 

[1] Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;School of Pharmacy, Ocean University of China, Qingdao 266003, China;School of Pharmacy, Fudan University, Shanghai 201203, China

关键词: c-Met;    synthesis;    kinase inhibitor;    3-carboxypiperidin-2-one;   

DOI  :  10.3390/molecules19022655

来源: mdpi

【 摘 要 】

A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC₅₀ values of 8.6−81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC₅₀s ranging from 0.57−16 μM.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.