Discovery of novel 1,2,4-triazolo-1,2,4-triazines with thiomethylpyridine hinge binders as potent c-Met kinase inhibitors

Aim: Mesenchymal–epithelial transition factor (c-Met)/HGF overactivation is involved in diverse human cancers. Materials & methods: Herein, we report the synthesis and biological evaluation of thiomethylpyridine-linked triazolotriazines as c-Met kinase inhibitors. Results: Compounds 10b and 11e were more potent than crizotinib on HepG2 cells with IC 50 values of 0.74 and 0.71 μM in the MTT assay, respectively. Interestingly, all of the...