Synthesis, Activity Evaluation, and Molecular Docking of 3‐Quinolin(one)ly‐[1,2,4]triazolo[4,3‐ b ][1,2,4,5]tetrazine Derivatives as c‐Met Inhibitors

Two series of [1,2,4]triazolo[4,3‐ b ][1,2,4,5]tetrazine derivatives have been synthesized and evaluated for their antitumor activities. These compounds exhibit potent antiproliferative activities against A549 and H460 cells and c‐Met kinase inhibitory activities. Five compounds are highly effective against A549 and H460 cells with IC 50 values in 2.97–16.50 μM (the mean ± SD value of three independent determinations). Molecular docking is further performed to study the inhibitor–c‐Met kinase interactions, and the results show that compound 3a is potently bound to the c‐Met kinase with three hydrogen bonds, one π‐‐‐π, and one CH‐‐‐π interactions. Based on the preliminary results, it is deduced that compound 3a with potent c‐Met kinase inhibitory activity may be a potential anticancer agent.