Research Progress on the Synthesis and Structure-Activity Relationship of Five Hypoglycemic Active Heterocycles Based on Dipeptidyl Peptidase 4 (DPP-4) Target Design

Abstract

Recently, diabetes has gradually become a main life-threatening disease in China. Drug targets for the treatment of diabetes mainly include dipeptidyl peptidase 4 (DPP-4), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPARγ) receptor and so on, in which targeted drug research targeting DPP-4 is a hot spot in recent years. DPP-4 inhibitor is a drug for the treatment of type 2 diabetes, and its biggest advantage is that it is not easy to induce hypoglycemia and increase weight. It is reported that the currently available DPP-4 targeted drugs can cause adverse reactions, such as pancreatitis and hypersensitivity. Therefore, it is worth further studying to continue to develop new hypoglycemic drugs for DPP-4 inhibitors to avoid adverse reactions. According to the systematic literature review, the potential heterocyclic structures with hypoglycemic activity are summarized and through computer molecular simulation docking, five kinds of heterocyclic structures with high hypoglycemic activity and easy synthesis are finally screened out based on DPP-4 target design. The synthesis routes and structure-activity relationships are summarized and analyzed, which provides a research basis for the development of safe, efficient and novel hypoglycemic drugs for DPP-4 inhibitors in the future. Keywords diabetes; dipeptidyl peptidase 4 (DPP-4) inhibitor; molecular docking; synthesis methods; structure-activity relationship