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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 IC50 values of 0.74 and 0.71 mu M in theMTT assay, respectively. Interestingly, all of the target compounds displayed IC50 values in the range of 3.9-11.1 nM in the c-Met kinase inhibition assay which were lower than the value for crizotinib (11.1 nM). Conclusion: Target compound 10b can be considered as a leading drug candidate due to its lower IC50 values than crizotinib in both HGF-induced proliferation and c-Met kinase inhibition assays. [GRAPHICS]

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles