A series of 6, 7-dimethoxy-4-(2-fluorophenoxy)quinoline derivatives containing piperazinamide were designed and synthesized as potential c-Met inhibitors based on cabozantinib and foretinib by modification on the intermediate chain. The structures of the new compounds were confirmed by MS and NMR. All novel target compounds were evaluated for their c-Met inhibitory activity and cytotoxicity against human colon cancer cells(HT-29), human lung cancer cells(H460), human non-small cell lung cancer cells(A549) and human gastric cancer cells(MKN-45) using ELISA(ELISA) and MTT assay. The results showed that the inhibitory activities of 4-(4-chlorophenyl)-N-[4-[(6, 7-dimethoxyquinolin-4-yl)oxy]-3-fluorophenyl]piperazine-1-carboxamide(1b), 4-(3-chlorophenyl)-N-[4-[(6, 7-dimethoxyquinolin-4-yl)oxy]-3-fluorophenyl]piperazine-1-carboxamide(1h) and 4-(2-chlorophenyl)-N-[4-[(6, 7-dimethoxyquinolin-4-yl)oxy]-3-fluorophenyl]piperazine-1-carboxamide(1j) against HT-29, H460, A549 and MKN-45 cells were significantly better than those of cabozantinib. And compounds 1h and 1j had strong c-Met inhibitory activities with IC_(50 )values of 0.007 2 and 0.009 8 μmol/L, resp.