Inhibitors of proline-specific dipeptidyl peptidases: DPP IV inhibitors as a novel approach for the treatment of Type 2 diabetes

Abstract

Dipeptidyl peptidase IV (DPP IV) is a validated target for the treatment of Type 2 diabetes, with several inhibitors currently in Phase III clinical trials. This review will mainly focus on DPP IV inhibitors that were published in scientific literature and patents after 2002. Medicinal chemistry aspects of several classes of inhibitors are described with respect to inhibitory potency, selectivity over DPP8, DPP9, FAPα and DPP II, stability and ADME/Tox issues. Although the main part of this review is on potent and selective DPP IV inhibitors, selective inhibitors for the related proline-specific dipeptidyl peptidases will be described.

Keywords::

• dipeptidyl peptidase IV (DPP IV)
• DPP II
• DPP8
• DPP9
• FAPα
• medicinal chemistry
• Type 2 diabetes