Novel N-substituted 4-hydrazino piperidine derivative as a dipeptidyl peptidase IV inhibitor

A novel class of N-substituted 4-hydrazino piperidine derivatives were designed, synthesized and evaluated for DPP IV inhibition. The SAR studies on the N-substituted piperidine led to the discovery of compound 22e as a potent DPP IV inhibitor (IC50 88 nM), which is highly selective over other peptidases. In vivo efficacy indicates that compound 22e stimulates insulin release in response to glucose load and improves glucose tolerance in n5-STZ and Zucker Diabetic Fatty (ZDF) rats.

Graphical abstractVarious N-substituted (4-hydrazino piperidine) derivatives were synthesized and screened for in vitro DPP IV inhibition. In vivo efficacy of compound 22e has also been carried out.Figure optionsDownload full-size imageDownload as PowerPoint slide