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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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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;Xin Zhai*
刊物名称
Archiv der Pharmazie
2017
350
2
e1600307-e1600307

{Author}: Jiao Wang;Lijun Xie;Yu Wang;Xiaoqiang Wang;Shuancheng Xi;Tianfang Zeng;Ping Gong;Xin Zhai*

{Journal}: Archiv der Pharmazie

{Year}: 2017

{Volume}: 350

{Issue}: 2

{Pages}:e1600307-e1600307

{Keywords}: Antitumor activity; QSAR; Synthesis; c-Met inhibitors

{Abstract}: 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.

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