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

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 IC 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 IC  = 1.52 nM) with IC values of 0.24, 0.45, and 0.13 µM against HT-29, MKN-45, and A549 cells, respectively.