4,5,6,7-Tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine as a new scaffold for heat shock protein 90 inhibitors

Heat shock protein 90 (hsp90) is a promising anticancer drug target. A library of 2,4-dihydroxyphenyl (resorcinol) substituted 4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine compounds that target this protein were designed and prepared based on our earlier study. The compounds were tested in five cancer cell lines and seven of them showed notable anticancer activity (IC50 2–10 μmol/L). The active subset compounds were further subjected to a polarized fluorescent assay and exhibited high binding affinity toward purified hsp90 (IC50 60–100 nmol/L). These results indicated that the tetrahydro-triazolopyrazine motif of the molecules may represent a novel scaffold for the development of hsp90 inhibitors.

2,4-Dihydroxyphenyl (resorcinol) substituted 4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine derivatives were found to be potent Hsp90 inhibitors and exhibited remarkable anti-cancer activities in vitro. The results indicated that the title compounds represent a novel class of hsp90 inhibitor.Figure optionsDownload as PowerPoint slide