Design, Synthesis, and Biological Evaluation of 4-Phenoxyquinoline Derivatives Containing Benzo[d]thiazole-2-yl Urea as c-Met Kinase Inhibitors

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• 作者：Hongrui Lei ; Gang Hu ; Yu Wang ; Pei Han ; Zijian Liu ; Yanfang Zhao and Ping Gong
• 刊名：Archiv der Pharmazie
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：349
• 期：8
• 页码：651-661
• 全文大小：1555K
• ISSN：1521-4184

文摘

A series of novel 4-phenoxyquinoline derivatives containing the benzo[d]thiazole-2-yl urea moiety were synthesized and evaluated for their cytotoxicity against the HT-29, MKN-45, and H460 cell lines. The structures of the target compounds were confirmed by ¹H NMR and MS spectra. Most of them showed moderate to excellent potency against the three tested cell lines. Especially, compound 23 was identified a promising agent (c-Met IC₅₀ = 17.6 nM), showing the most potent anticancer activities with IC₅₀ values of 0.18, 0.06, and 0.01 µM against the HT-29, MKN-45, and H460 cell lines, respectively. The docking results of 23 with the c-Met kinase model 3LQ8 showed a specific binding mode between the ligand and the target protein.