Design, Synthesis, and Biological Evaluation of [1,2,4]triazolo[4,3-a] Pyrazine Derivatives as Novel Dual c-Met/VEGFR-2 Inhibitors.

ABSTRACT: In this study, we designed and synthesized a series of novel [1,2,4]triazolo [4,3-a]pyrazine derivatives, and evaluated them for their inhibitory activities toward c-Met/VEGFR-2 kinases and antiproliferative activities against tested three cell lines in vitro. Most of the compounds showed satisfactory activity compared with lead compound foretinib. Among them, the most promising compound 17l exhibited excellent antiproliferative activities against A549, MCF-7, and Hela cancer cell lines with IC₅₀ values of 0.98 ± 0.08, 1.05 ± 0.17, and 1.28 ± 0.25 µM, respectively, as well as excellent kinase inhibitory activities (c-Met IC₅₀ = 26.00 nM and VEGFR-2 IC₅₀ = 2.6 µM). Moreover, compound 17l inhibited the growth of A549 cells in G0/G1

SUBMITTER: Liu X 

PROVIDER: S-EPMC9019572 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature