Design, Synthesis and Structure-activity Relationship Study of 3-Aryl-5-triazolyl-oxadiazole Derivatives as Hypoxia-inducible Factor-1 Inhibitors

OBJECTIVE To design and synthesize a series of 3-aryl-5-triazolyl-oxadiazole derivatives as hypoxia- inducible factor 1(HIF-1) inhibitors. METHODS Taking compound 8 as the guide, the pyrazolyl group was replaced with 1,2,3-triazole group, and the oxadiazole and benzene ring substituents were modified to obtain a novel series of 3-aryl-5-triazole group oxadiazole derivatives. RESULTS Most of these newly designed compounds showed good HIF-1 inhibitory activities and compound 10n was the most potent inhibitor with IC₅₀ value of 0.59 μmol·L^-1. Its mechanism of action was to inhibit the expression of HIF-1α protein, and could significantly inhibit the invasion and migration of SKOV3 cells. CONCLUSION The series of 3-aryl-5-triazolyl-oxadiazole derivatives are new HIF-1 inhibitors, showing the effect of inhibiting tumor migration.