Seco-prolinenitrile inhibitors of dipeptidyl peptidase IV define minimal pharmacophore requirements at P1

A series of seco-prolinenitrile-containing dipeptides were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV, a promising new target for treatment of type 2 diabetes. The inhibitors described herein assess the minimum structural requirements at P1 for this enzyme, resulting in the identification of inhibitors with low nM potency.

Graphical abstractThe synthesis and dipeptidyl peptidase IV inhibitory activity of glycine- and alaninenitrile dipeptides are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide