title: DPP-4 inhibitors: a patent review (2012 - 2014).
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Università di Chieti-Pescara "G. d'Annunzio", Dipartimento di Farmacia , Via dei Vestini 31, 66100, Chieti , Italy +08713554476 ; +08713554476 ; a.mollica@unich.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Costante
authors.forename: Azzurra
authors.initials: A
authors.lastname: Stefanucci
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010330:Patents as Topic
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D018819:Dipeptidyl Peptidase 4
keywords: CD26; dipeptidyl peptidase 4 inhibitors; incretin system; type 2 diabetes mellitus