Synthesis and evaluation of a series of pyridine and pyrimidine derivatives as type II c-Met inhibitors

Publication date: Available online 5 April 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yanmei Zhao, Jiankang Zhang, Rangxiao Zhuang, Ruoyu He, Jianjun Xi, Xuwang Pan, Yidan Shao, Jinming Pan, Jingjing Sun, Zhaobin Cai, Shourong Liu, Weiwei Huang, Xiaoqing Lv
In this study, a series of novel pyridine and pyrimidine-containing derivatives were designed, synthesized and biologically evaluated for their c-Met inhibitory activities. In the biological evaluation, half of the target compounds exhibited moderate to potent c-Met inhibitory activities. Among which, it is noteworthy that compounds 13d not only showed most potent c-Met inhibitory potency but also displayed excellent anti-proliferative activity (IC50 = 127 nM against EBC-1 cell line) as well as an acceptable kinase selectivity profile. Moreover, the western blot assay indicated that 13d inhibited c-Met phosphorylation in EBC-1 cells in a dose-dependent manner, with complete abolishment at 0.1 mM. All these experimental results suggested that 13d could be served as a promising lead compound for the development of anticancer agents.

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