Discovery and biological evaluation of novel 6,7-disubstituted-4-(2-fluorophenoxy) quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety as c-Met kinase inhibitors

作者：Zhou, Shunguang; Liao, Huimin; Liu, Mingmei; Feng, Guobing; Fu, Baolin; Li, Ruijuan; Cheng, Maosheng; Zhao, Yanfang^*; Gong, Ping

来源：Bioorganic & Medicinal Chemistry, 2014, 22(22): 6438-6452.

DOI：10.1016/j.bmc.2014.09.037

• Receptor tyrosine kinase
• c-Met
• Antitumor activity
• Quinoline derivatives
• 1,2,3-Triazole-4-carboxamide

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 biological activities against c-Met kinase and five typical cancer cell lines (A549, H460, HT-29, MKN-45 and U87MG). Most compounds showed moderate to excellent antiproliferative activity. In this study, a promising compound 34, with a c-Met IC50 value of 1.04 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The SAR analyses indicated that compounds with halogen group, especially fluoro group, at 4-position on the phenyl ring (moiety B) have potent antitumor activity, and methylation on the 5-atom linker played an important role in the c-Met enzymatic activity.

• 出版日期2014-11-15
• 单位沈阳药科大学