Zhang_2013_Chem.Biol.Drug.Des_81_198

Dipeptidyl peptidase-4 inhibitors hold great potential for the treatment of type 2 diabetes. A series of 1-(gamma-1,2,3-triazol substituted prolyl)-(S)-3,3-difluoropyrrolidines were designed, synthesized, and evaluated as novel dipeptidyl peptidase-4 inhibitors. Most of the compounds exhibited good in vitro potency against dipeptidyl peptidase-4. Among these, compounds 7j, 7q, and 7s displayed good dipeptidyl peptidase-4 activity and excellent selectivity versus other proteases including dipeptidyl peptidase-8, dipeptidyl peptidase-9, and FAP. The possible binding modes of compounds 7j, 7q, and 7s with dipeptidyl peptidase-4 were also explored by molecular docking simulation.