By 2030, the World Health Organization predicts more than 300 million people to be diagnosed with type 2 diabetes. The current therapeutic agents (like Insulin, Sulphonylureas, Biguanides, �±-Glucosidase inhibitors, PPAR agonist and GLP-1 agonist), although effective in increasing insulin secretion, are associated with some safety issue and undesirable side effects, including hypoglycemia, abnormalities in cardiovascular responses and �²-cell apoptosis. DPP-4 inhibitors offer several potential advantages over existing therapies including decreased risk of hypoglycemia, potential for weight loss and the potential for regeneration and differentiation of pancreatic �²-cells. Moreover, DPP-4 inhibitors can also be administered orally. Hence, Dipeptidyl peptidase-4 (DPP-4) inhibitors are new promising strategy for antidiabetic activity and several drugs are in the developmental stage. The present work involves the synthesis of 2-cyano pyrrolidine derivatives. Among all DPP-4 inhibitor derivatives, 2-Cyano pyrrolidine-based inhibitors have been studied most extensively. Apart from behaving as a proline mimic, the presence of the nitrile on the five-membered ring was shown to provide (i) nanomolar inhibition of DPP-4 and (ii) chemical stability adequate for oral administration. These intermediates fused with quinazolin-4-one derivative. The synthesized DPP-4 inhibitor derivative was evaluated by fluorescence assay using Gly-Pro-AMC as a DPP-4-specific fluorescent substrate.
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