Design and biological evaluation of novel 4-(2-fluorophenoxy)quinoline derivatives bearing an imidazolone moiety as c-Met kinase inhibitors

作者：Liao, Weike; Hu, Gang; Guo, Zhuang; Sun, Deyu; Zhang, Lixia; Bu, Yanxin; Li, Yingxiu; Liu, Yajing^*; Gong, Ping

来源：Bioorganic & Medicinal Chemistry, 2015, 23(15): 4410-4422.

DOI：10.1016/j.bmc.2015.06.026

• c-Met
• Antitumor activity
• Quinoline derivatives
• Imidazolone-4-carboxamide

A series of 4-(2-fluorophenoxy) quinoline derivatives containing an imidazolone moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, H460, HT-29 and MKN-45). Most compounds showed moderate to excellent activities in enzyme and cellular assays. The most promising analog, 58 (c-Met IC50 = 1.42 nM), displayed 2.1-, 8.6-fold increase against H460, and MKN-45 cell lines, respectively, compared with foretinib. An analysis of structure-activity relationships revealed that an ortho substituted phenyl ring as well as an N-unsubstituted imidazolone linker is favorable for antitumor activity.

• 出版日期2015-8-1
• 单位辽宁省肿瘤医院; 沈阳药科大学