Design and Synthesis of Novel 4-Phenoxyquinolines Bearing 3-Hydrosulfonylacrylamido or 1H-Imidazole-4-carboxamido Scaffolds as c-Met Kinase Inhibitors

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• 作者：Jiao Wang ; Lijun Xie ; Yu Wang ; Xiaoqiang Wang ; Shuancheng Xi ; Tianfang Zeng ; Ping Gong and Xin Zhai
• 刊名：Archiv der Pharmazie
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：350
• 期：2
• 全文大小：1641K
• ISSN：1521-4184

文摘

A series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives bearing (E)-3-hydrosulfonylacrylamido or 1H-imidazole-4-carboxamido moieties were designed, synthesized and evaluated for their cytotoxicity against A549, MKN-45, and HT-29 cancer cell lines in vitro. All the target compounds showed moderate to significant cytotoxic activity against the tested cells with IC₅₀ values ranging from 0.13 to 2.65 µM. Five of them were further examined for their inhibitory activity against c-Met kinase, which identified compound 30 as a promising agent (c-Met IC₅₀ = 1.52 nM) with IC₅₀ values of 0.24, 0.45, and 0.13 µM against HT-29, MKN-45, and A549 cells, respectively.