Recent Medicinal Chemistry Approach for the Development of Dipeptidyl Peptidase IV Inhibitors

Abstract

Background: Diabetes, a metabolic disease occurs due to decrease or no effect of insulin on blood glucose level. Current oral medication stimulates insulin release, increase glucose absorption and its utilization as well decrease hepatic glucose output. Two major incretin hormones like Glucose dependent insulinotropic polypeptide (GIP) and glucagon like peptide – 1 (GLP -1) stimulate insulin release after meal but their action is inhibited by enzyme dipeptidyl peptidase- IV. Objective: The activity of endogenous GLP-1 and GIP prolong and extend with DPP IV inhibitors which are responsible for stimulation of insulin secretion and regulate blood glucose level. DPP IV inhibitors have shown effectiveness and endurability with neutral effect on weight as well as less chances of hypoglycemia in management of type 2 diabetes. These journeys have been started from Sitagliptin (marketed in 2006) to Evogliptin (marketed in 2015, Korea). Conclusion: Treatment of type 2 diabetes includes lifestyle changes, oral medications, and insulin. Newer and superior therapies are required than presently prescribed drugs. Various heterocyclic derivatives have been tried but due to masking of DASH proteins, CYP enzymes and hERG channel, they showed side effects. Based on these, study has been focused on the development of safe, influential, selective and long-lasting inhibitors of DPP IV.