Synthesis Of Potent Dipeptidyl Peptidase Ⅳ Inhibitors Derived From β-aminoamides Bearing New Substituted Triazolopiperidines

The functional mechanism and development of dipeptidyl peptidase IV inhibitors were discussed in this issue. We selected Sitagliptin as the lead compound to acquire the active group and became interested in modifying the 1,2,4-triazole group of Sitagliptin to 1,2,3-trizole group to obtain 14 the triazolopiperazine compounds as the novel DPP-4 inhibitors. We mainly investigated the synthesis, SARs and biological properties of this type of compounds, designed and completed the synthetic routes. All the structure of compounds was confirmed by mass spectrum and HNMR. We studied activity selection in vitro and metabolism experiment in vivo in order to obtain the potenter new candidate than Sitagliptin.Pharmacological experiment indicated that most compounds exhibited excellent in vitro activity. Among these, selected compounds were further subjected to pharmacokinetic study. The potenter compounds were undergoing oral glucose tolerance test (OGTT) in our laboratory.