Twenty-seven novel 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives were designed and synthesized. 1H-Imidazole-4-carboxamido and (E)-3-hydrosulfonylacrylamido linkers were designed. The configurations of compounds 32–42 were unequivocally confirmed as the E isomer. The compound 16 demonstrated remarkably better biological property and c-Met kinase inhibition than Foretinib. Molecular docking analysis was supplied to guide and explain the observed SARs as well.