Recent patents of dipeptidyl peptidase IV inhibitors.

INTRODUCTION

The serine exopeptidase DPP IV is a dual protein able to work as an enzyme and an interacting protein. The incretin molecules glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are hydrolyzed by DPP IV into inactive forms, which are unable to promote insulin secretion. Therefore, DPP IV is a validated target for the treatment of type 2 diabetes mellitus (T2DM), and a number of inhibitors have been reported in the literature as antidiabetic drugs.

AREAS COVERED

DPP IV inhibitor patents from 2006 are included in this review. Documents are classified into chemical groups depending on the main claim. Groups are: i) pyrrolidines and thiazolidines; ii) cyclohexanes, piperidines, piperazines, pyridines and pyrimidines; iii) fused 5-carbon cycles; iv) pyridine, pyrimidine and pyrazine-based bicyclic structures; v) indoles, condensed-imidazoles and xanthines; vi) pyrido-pyrimidines, quinolones, isoquinolines, quinozalines, quinoxalines, naphthyridines, quinolones and quinazolinones; vii) benzoquinolizines, fused aminopiperidines and fused triazoles; viii) other heterocyclic structures and ix) peptidomimetics.

EXPERT OPINION

Research in finding new DPP IV inhibitors is intense, despite the number of reported molecules. This is mainly because marketed compounds have been approved in the last 5 years and long-term side effects have not been detected. The perfect inhibitor for the T2DM treatment would therefore be a molecule that inhibits GLP-1 and GIP degradation by DPP IV, but does not affect the activity of the protease in other substrates, nor disturbs the communication of DPP IV with other proteins.