Discovery of a novel 6,7-disubstituted-4-(2-fluorophenoxy)quinolines bearing 1,2,3-triazole-4-carboxamide moiety as potent c-Met kinase inhibitors

• DOI: 10.1016/j.ejmech.2016.04.035
• Publication Date: 2016-04-30T10:21:02Z
• Authors: Mingmei Liu; Yunlei Hou; Weile Yin; Shunguang Zhou; Ping Qian; Zhuang Guo; Liying Xu; Yangfang Zhao
• Keywords: Moiety; Carboxamide; Quinoline; Triazole; IC50; 1,2,3-Triazole; Structure–activity relationship

A series of 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety were designed, synthesized and evaluated for their in vitro cytotoxic activities against four typical cancer cell lines (A549, H460, HT-29, and MKN-45). Most compounds showed moderate-to-excellent antiproliferative activity. Compounds 32, 36, 37, 45, 51, and 52 were further examined for their inhibitory activity against c-Met kinase. The promising compound 37, with a c-Met IC50 value of 2.27 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The analysis of their structure-activity relationships indicated that compounds with EWGs, especially chloro group, at 2-position on the phenyl ring (moiety B) have potent antitumor activity.