Design, Synthesis, Structure–Activity Relationships, and Docking Studies of 1‐(γ‐1,2,3‐Triazol Substituted Prolyl)‐( S )‐3,3‐Difluoropyrrolidines as a Novel Series of Potent and Selective Dipeptidyl Peptidase‐4 Inhibitors

Dipeptidyl peptidase‐4 inhibitors hold great potential for the treatment of type 2 diabetes. A series of 1‐(γ‐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.