Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (4): 1029-1036.DOI: 10.6023/cjoc201811030 Previous Articles     Next Articles



付洋a,b, 盛丽c, 高立信c, 李佳c, 孙良鹏a   

  1. a 延边大学医学院 延吉 133002;
    b 中国科学院长春应用化学研究所 长春 130000;
    c 中国科学院上海药物研究所 国家新药筛选中心 上海 201203
  • 收稿日期:2018-11-26 修回日期:2018-12-21 发布日期:2019-01-10
  • 通讯作者: 李佳, 孙良鹏;
  • 基金资助:


Synthesis and PTP1B Inhibitory Activity of Novel Chalcone Derivatives Bearing 1H-Benzo[d]imidazol or 1H-Benzo[d][1,2,3]triazol Moieties

Fu Yanga,b, Sheng Lic, Gao Lixinc, Li Jiac, Sun Liangpenga   

  1. a Medical College, Yanbian University, Yanji 133002;
    b Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130000;
    c National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
  • Received:2018-11-26 Revised:2018-12-21 Published:2019-01-10
  • Contact: 10.6023/cjoc201811030;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos.81460524,81773779) and the Scientific Research Fund Project of Education Department of Jilin Province (No.2015-50).

Protein tyrosine phosphatase 1B (PTP1B) inhibitor has recently been identified as new candidate drug for type Ⅱ diabetes and obesity due to it is a negative regulator of the insulin and leptin-signaling pathway. In order to find new nonphosphonate-based pTyr mimetics, a series of novel chalcone derivatives bearing 1H-benzo[d]imidazol or 1H-benzo[d] [1,2,3]-triazol moieties were designed, synthesized, and evaluated for their PTP1B inhibitory activities. The results demonstrated that all compounds presented potent inhibitory activities against PTP1B, among which 2-(1H-benzo[d] [1,2,3]triazol-1-yl)-N'-(4-(3-(naphthalen-2-yl)-3-oxoprop-1-en-1-yl)benzylidene)acetohydrazide (10i) exhibited the best potency with IC50 value of (2.98±0.04) μmol·L-1. Importantly, 2-(1H-benzo[d] [1,2,3]triazol-1-yl)-N'-(4-(3-oxo-3-(p-tolyl)prop-1-en-1-yl)benzylidene)-acetohydrazide (10h) showed no significant inhibition on T-cell protein tyrosine phosphatase (TCPTP) at the concentration of 20 μg/mL, suggesting the highly selectivity of this agent toward PTP1B.

Key words: PTP1B inhibitor, 1H-benzo[d]imidazol, 1H-benzo[d] [1,2,3]triazol, chalcone