Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration

A series of 5β-methylprolyl-2-cyanopyrrolidine analogs were synthesized and identified as long-acting DPP-IV inhibitors. The mode of binding and the effect on the plasma glucose level were evaluated. A series of 5β-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure–activity relationships are also presented.