Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents

This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, & beta;-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. The structural activities of the various scaffolds against DPP-4 were further illustrated by their inhibitory concentration (IC50) values. Additionally, various synthesis schemes were developed to make several commercially available DPP4 inhibitors such as vildagliptin, sitagliptin and omarigliptin. In conclusion, the use of halogenated scaffolds for the development of DPP-4 inhibitors is likely to be an area of increasing interest in the future.

Automated summary

This article discusses various scaffolds that can be used to develop DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). The study highlights different scaffolds with high DPP-4 inhibition activity and explains the potential enhancement by substituting certain atoms. Docking experiments were performed on existing drugs and their interaction with specific residues was studied. The article also describes the synthesis schemes for commercially available DPP-4 inhibitors. Overall, the use of halogenated scaffolds for developing DPP-4 inhibitors is an area of increasing interest.