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Bioorg Med Chem. 2017 Jun 15;25(12):3195-3205. doi: 10.1016/j.bmc.2017.04.003. Epub 2017 Apr 5.

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

Author information

1
Department of Pharmaceutical Preparation, Hangzhou Xixi Hospital, Hangzhou 310023, Zhejiang Province, China.
2
College of Medicine, Jiaxing University, Jiaxing 314001, Zhejiang Province, China. Electronic address: lxqd1@126.com.

Abstract

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=127nM 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 0.1mM. All these experimental results suggested that 13d could be served as a promising lead compound for the development of anticancer agents.

KEYWORDS:

Anti-cancer; Inhibitor; Pyridine; Pyrimidine; Type II; c-Met

PMID:
28412159
DOI:
10.1016/j.bmc.2017.04.003
[Indexed for MEDLINE]

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