DPP-4 inhibitors: a patent review (2012 - 2014)

Dipeptidyl peptidase 4 (DPP-4) is a serine protease, which catalyzes the hydrolytic process of the amide bond X-Ala or X-Pro at the N-terminus of peptides. This enzyme is involved in the degradation of two incretin hormones glucagon-like peptide-1 and glucose-dependent-insulinotropic polypeptide, which increase the production and release of insulin. Therefore, DPP-4 inhibitors are considered as one of the well-established therapies available for type 2 diabetes mellitus.

In this review, the authors report all the patents related to DPP-4 inhibitors from 2012 to 2014. The chemical-related patents have been divided in three general families: i) peptidomimetics; ii) peptides; and iii) non-peptidomimetics compounds. The third group is the most consistent; thus the patents have been further divided on the basis of the chemical structure. In the last section, we briefly discuss the patents containing the formulations or associations of DPP-4 inhibitors with other drugs.

In the last few years, the research on DPP-4 inhibitors has significantly grown leading to the development of heterocyclic scaffolds and non-peptidomimetic structures. Unfortunately, these compounds are not immune from side effects associated with the inhibition of other substrates, indicating that DPP-4 inhibitors are likely multi-target drugs. Therefore, their potential multi-target effects require more attention in clinical practice, even if at this moment, all the patents are focused only on diabetes.