Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (9): 2142-2149.DOI: 10.6023/cjoc201603045 Previous Articles     Next Articles



王文龙a, 骆欢a, 高雅a, 高立信b, 盛丽b, 周宇波b, 李佳b, 李静雅b, 冯柏年a   

  1. a 江南大学药学院 无锡 214122;
    b 中国科学院上海药物研究所 国家新药筛选中心 新药研究国家重点实验室 上海 201203
  • 收稿日期:2016-03-28 修回日期:2016-04-27 发布日期:2016-05-17
  • 通讯作者: 李静雅, 冯柏年;
  • 基金资助:


Synthesis of Aromatic Amide Derivatives and Their Biological Evaluation against Protein Tyrosine Phosphatase 1B and Scr Homology-2 Domain Containing Protein Tyrosine Phosphatase-2

Wang Wenlonga, Luo Huana, Gao Yaa, Gao Lixinb, Sheng Lib, Zhou Yubob, Li Jiab, Li Jingyab, Feng Bainiana   

  1. a School of Pharmaceutical Science, Jiangnan University, Wuxi 214122;
    b State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
  • Received:2016-03-28 Revised:2016-04-27 Published:2016-05-17
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No.21472069) and the State Key Laboratory of Drug Research (No.SIMM1302KF-05).

To explore the chemical space of protein tyrosine phosphatase 1B (PTP1B) inhibitors by changing bis-aromatic amide moiety into aromatic amide moiety, a series of aromatic amide derivatives were designed, synthesized and their biological activities were evaluated against PTP1B and Scr homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). Among them, compound 3c displayed moderate inhibitory activity with IC50 of (5.13±0.21) μmol/L against PTP1B and showed two times selectivity for other related PTPs. Interestingly, compound 12[IC50=(7.47±1.26) μmol/L] showed moderate inhibitory activity against SHP2 and 2-fold selectivity against PTP1B, T-cell protein tyrosine phosphatase (TCPTP) or Src homology-2 domain containing protein tyrosine phosphatase-1 (SHP1) respectively, and offered a novel scaffold to develop new SHP2 inhibitors.

Key words: PTP1B, SHP2, aromatic amide derivatives, inhibitors