Design, synthesis and anti-diabetic activity of novel 1, 2, 3-triazole-5-carboximidamide derivatives as dipeptidyl peptidase-4 inhibitors

Abstract The inhibitors of the enzyme dipeptidyl peptidase type 4 (DPP-4), as a potent stimulator of insulin secretion and an inhibitor of glucagon secretion from the pancreas, have been considered as promising agents for the treatment of type 2 diabetes mellitus. In this study, a novel series of 1, 2, 3-triazole-5-carboximidamide derivatives were designed, synthesized, and inhibitory activity evaluated against the DPP-4 enzyme. All of the compounds represented inhibitory activity, and among them, compounds 6a, 6b, and 6c showed desirable inhibitory activity of DPP-4 with IC50 values of 14.75 nM, 6.75 nM, and 6.57 nM, respectively. Compound 6a with a dose of 10 mg/kg showed glucose tolerance enhancement during OGTT in NMRI mice. Moreover, chronic treatment of Wistar rats for 14 days with compound 6a showed a significant decrease in blood glucose levels of diabetic rats, which was similar to sitagliptin as a standard.