Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (3): 770-784.DOI: 10.6023/cjoc202107001 Previous Articles     Next Articles


基于二肽基肽酶4 (DPP-4)靶点设计的五种降糖活性杂环合成及构效关系研究进展

孔媛芳a, 杨彬a, 庄严a, 张京玉a, 孙德梅a,*(), 董春红b,*()   

  1. a 河南中医药大学药学院 郑州 450046
    b 河南中医药大学中医药科学院 郑州 450046
  • 收稿日期:2021-07-01 修回日期:2021-09-30 发布日期:2021-11-09
  • 通讯作者: 孙德梅, 董春红
  • 基金资助:
    河南中医药大学仲景高层次人才专项基金(00104311-2021-1-8); 河南省高等学校重点科研项目(20A350004); 河南省自然科学基金(202300410264)

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

Yuanfang Konga, Bin Yanga, Yan Zhuanga, Jingyu Zhanga, Demei Suna(), Chunhong Dongb()   

  1. a College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046
    b Academy of Chinese Medical Science, Henan University of Chinese Medicine, Zhengzhou 450046
  • Received:2021-07-01 Revised:2021-09-30 Published:2021-11-09
  • Contact: Demei Sun, Chunhong Dong
  • Supported by:
    Zhongjing Scholars Research Funding of Henan University of Chinese Medicine(00104311-2021-1-8); Key Scientific Research Projects of Colleges and Universities in Henan Province(20A350004); Natural Science Foundation of Henan Province(202300410264)

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.

Key words: diabetes, dipeptidyl peptidase 4 (DPP-4) inhibitor, molecular docking, synthesis methods, structure-activity relationship