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

Abstract

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.

Potential Dual Mechanism of Hypouricemicactivity of DPP-4 Inhibitors With Purine-Based Scaffold

“…Some DPP-4 inhibitors (13)(14)(15)(16)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) have been derived from a xanthine scaffold, similar to the structure of linagliptin (Table 1, Figure 3). 61 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 61 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 ...…”

“…DPP-4 inhibitors with purine scaffold structurally little different from the above listed representatives with reported IC50 values of 10 nM, 89 nM and 6 pM, respectively(21,24,28) …”

Teneligliptin: a review on cardio-renal safety

“…The cardiovascular (CV) effects may be due to the fact that DPP4 inhibitors have multiple targets, leading to undesirable effects with the inhibition of various substrates. 13 Patients with type 2 diabetes mellitus frequently develop renal function impairment. DPP-4 inhibitors vary in their mode of excretion due to their different pharmacokinetic profile in patients with impaired kidney function should therefore be either avoided or a dose adjustment should be done in diabetic patients with CKD.…”

Dipeptidyl Peptidase‐4 Is a Target Protein of Epigallocatechin‐3‐Gallate

“…Accordingly, DPP4 inhibitors have clinical benefits in patients with diabetes mellitus [12]. A great number of DPP4 inhibitors with novel structures and high activity and selectivity have been reported, which can be divided into three categories: peptidomimetics, peptides, and nonpeptidomimetic compounds; many of them have been designed based upon the inhibitory potency, absorption, oral bioavailability, selectivity, and half-life [13]. In addition to blood glucose regulation, DPP4 inhibitors may also have extra-glycemic effects such as myocardial protection, lowering blood pressure, reducing the expression of local inflammatory factors, and improving vascular endothelial function [14].…”

“…In addition to blood glucose regulation, DPP4 inhibitors may also have extra-glycemic effects such as myocardial protection, lowering blood pressure, reducing the expression of local inflammatory factors, and improving vascular endothelial function [14]. However, side effects such as hemolysis, angioedema, and rheumatoid arthritis have also been observed [13]. erefore, there is interest in dietary therapies for the prevention and treatment of diabetes without adverse reactions.…”