Selenium Dioxide–Mediated Synthesis of Fused 1,2,4-Triazoles as Cytotoxic Agents

A series of fused 1,2,4-triazoles has been prepared by oxidative intramolecular cyclization of heterocyclic hydrazones with selenium dioxide. General applicability of this practical protocol was confirmed by the synthesis of moderate to high yields of 1,2,4-triazolo[4,3-a]pyridines, 1,2,4-triazolo[4,3-a]pyrimidines, 1,2,4-triazolo[4,3-a]pyramidines and 1,2,4-triazolo-[4,3-a]quinoxa lines. All compounds were tested in vitro for their cytotoxic activity against HCT-116, A549 and Colo-205 cell lines. Two compounds, 3-(4-methoxyphenyl)-7-methyl-[1,2,4]triazolo[4,3-a]pyridine and 1-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]quinoxaline, showed potent antiproliferative activity against the three cell lines.