Discovery of conformationally rigid 3-azabicyclo[3.1.0]hexane-derived dipeptidyl peptidase-IV inhibitors

The induction of conformationally restricted N-(aryl or heteroaryl)-3-azabicyclo[3.1.0]hexane derivatives at P2 region of compounds of 2-cyanopyrrolidine class was explored to develop novel DPP-IV inhibitors. The synthesis, structure–activity relationship, and selectivity against related proteases are delineated.

Graphical abstractNovel and conformationally-rigid 3-azabicyclo[3.1.0]hexan-6-amine derivatives were investigated as P2 amino partners in the cyanopyrrolidine class for DPP-IV inhibition.Figure optionsDownload full-size imageDownload as PowerPoint slide