Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (8): 3157-3170.DOI: 10.6023/cjoc202102046 Previous Articles     Next Articles


新型含咔唑环芳氨基乙酰腙衍生物的合成及其蛋白酪氨酸磷酸酶1B (PTP1B)抑制活性评价

李英俊a,*(), 林乐弟a, 靳焜b, 高立信c, 盛丽c, 刘季红d, 李佳c,*()   

  1. a 辽宁师范大学化学化工学院 辽宁大连 116029
    b 大连理工大学精细化工国家重点实验室 辽宁大连 116012
    c 中国科学院上海药物研究所 国家新药筛选中心 药物研究国家重点实验室 上海 201203
    d 大连理工大学化学分析测试中心 辽宁大连 116023
  • 收稿日期:2021-02-24 修回日期:2021-04-02 发布日期:2021-05-14
  • 通讯作者: 李英俊, 李佳
  • 基金资助:

Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Arylaminoacetylhydrazone Derivatives Containing Carbazole Moiety

Yingjun Lia(), Ledi Lina, Kun Jinb, Lixin Gaoc, Li Shengc, Jihong Liud, Jia Lic()   

  1. a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, Liaoning 116029
    b State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, Liaoning 116012
    c State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
    d Chemistry Analysis and Inspection Center, Dalian University of Technology, Dalian, Liaoning 116023
  • Received:2021-02-24 Revised:2021-04-02 Published:2021-05-14
  • Contact: Yingjun Li, Jia Li
  • Supported by:
    Natural Science Foundation of Liaoning Province(20102126)

In order to find novel protein tyrosine phosphatase 1B (PTP1B) inhibitors, a series of novel arylaminoacetylhydrazone derivatives containing carbazole moiety were designed and synthesized. Their structures and configurations were confirmed by IR, 1H NMR, 13C NMR, two-dimensional NMR spectra (including 1H-1H COSY, 1H-13C HMBC and NOESY) and elemental analysis. The inhibitory activities of all the target compounds against PTP1B were tested, and it was found that the target compounds had potent inhibitory activity against PTP1B, and most of them had lower IC50 value than the positive control drug oleanolic acid. Among them, N'-(9-octylcarbazol-3-ylmethylene)-2-(4-nitrophenylamino)acetohydrazide (3t) had the highest inhibitory activity against PTP1B with IC50 of (2.78±0.04) μmol/L. Molecular docking was used to study the bind of compound 3t with PTP1B enzyme.

Key words: protein tyrosine phosphatase 1B (PTP1B) inhibitor, carbazole, arylaminoacetylhydrazone, synthesis, molecular docking