Design and synthesis of long-acting inhibitors of dipeptidyl peptidase IV

A series of (4-substituted prolyl)prolinenitriles were synthesized and evaluated as inhibitors of dipeptidylpeptidase IV (DPP-IV). Among those tested, the 4β-[4-(hydroxyphenyl)prolyl]prolinenitriles showed a potent inhibitory activity with a long duration of action. Metabolic formation of the corresponding phenol glucuronates was found to contribute to their long duration of action. The activity profiles of the synthesized compounds are reported and structure–activity relationships are also presented.

The 4β-[4-(hydroxyphenyl)prolyl]prolinenitriles were synthesized and evaluated as inhibitors of dipeptidylpeptidase IV (DPP-IV). Metabolic formation of the corresponding phenol glucuronates was found to contribute to their long duration of action.Figure optionsDownload as PowerPoint slide