Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (8): 3204-3213.DOI: 10.6023/cjoc202103056 Previous Articles     Next Articles


烷基酚类死亡相关凋亡诱导蛋白激酶2 (DRAK2)小分子抑制剂的设计与合成研究

张正a,b, 戴成球a,c, 吴红红a,b, 李静雅a,b,*(), 南发俊a,b,*()   

  1. a 中国科学院大学 北京 100049
    b 中国科学院上海药物研究所 上海 201203
    c 杭州高等研究院 杭州 310024
  • 收稿日期:2021-03-29 修回日期:2021-04-29 发布日期:2021-05-14
  • 通讯作者: 李静雅, 南发俊

Design and Synthesis of Alkyl Phenols Inhibitors of Death Associated Apoptotic Protein Kinase 2 (DRAK2)

Zheng Zhanga,b, Chengqiu Daia,c, Honghong Wua,b, Jingya Lia,b(), Fajun Nana,b()   

  1. a University of Chinese Academy of Sciences, Beijing 100049
    b Shanghai Institute of Materia Medica, Shanghai 201203
    c Hangzhou Institute for Advanced Study, Hangzhou 310024
  • Received:2021-03-29 Revised:2021-04-29 Published:2021-05-14
  • Contact: Jingya Li, Fajun Nan

Death associated apoptotic protein kinase 2 (DRAK2) is a threonine/serine kinase and a member of the death- associated protein kinase (DAPK) family. Under the action of external stimuli, its overexpression has the ability to induce apoptosis. High glucose, high fat, and certain cellular inflammatory factors can induce the high expression of DRAK2, thereby causing pancreatic β-cell apoptosis. DRAK2 may play a mediating role in the process. Therefore, small molecule inhibitors targeting DRAK2 own good development prospects to treat diabetes. In this work, more than 20 active compounds were obtained through structural modification of the alkylphenols compound 8a, and the structure-activity relationship between them was preliminarily determined.

Key words: death associated apoptotic protein kinase 2, diabetes, alkylphenols, inhibitors