Discovery of Potent c-MET Inhibitors with New Scaffold Having Different Quinazoline, Pyridine and Tetrahydro-Pyridothienopyrimidine Headgroups

作者：Jiang, Yingnan; Zhang, Ke; Gao, Suyu; Wang, Guihua; Huang, Jian; Wang, Jinhui^*; Chen, Lixia^*

来源：Molecules, 2016, 21(5): 612.

DOI：10.3390/molecules21050612

• quinazoline
• pyridine
• tetrahydro-pyridothienopyrimidine
• MET inhibitor
• cancer therapy

Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N-1-(3-fluoro-4-methoxyphenyl)-N-3-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c-MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy.

• 出版日期2016-5
• 单位沈阳药科大学