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

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 1 H 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 IC 50  = 17.6 nM), showing the most potent anticancer activities with IC 50 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.