Potent non-nitrile dipeptidic dipeptidyl peptidase IV inhibitors

The synthesis and structure–activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with β-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S,3R)-2,3-methanopyrrolidine based scaffold.

Graphical abstractEnzyme inhibitory activity of a series of non-nitrile dipeptides help to discern the nature of individual SAR contributions from P1 and P2 of dipeptide derived DPP4 inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide