Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (6): 1363-1369.DOI: 10.6023/cjoc201412027 Previous Articles     Next Articles


一种磷酸酪氨酸拟似物类蛋白酪氨酸磷酸酶1B 抑制剂的合成及体外活性评价

周晓伟a, 唐延婷b, 桑锋c, 张秀利a, 李立新b, 周红刚c, 刘伟d, 戴玉洁a   

  1. a 天津科技大学生物工程学院 天津 300457;
    b 天津国际生物医药联合研究院高通量药物筛选中心 天津 300457;
    c 南开大学药学院 天津 300071;
    d 天津科技大学理学院 天津 300457
  • 收稿日期:2014-12-16 修回日期:2015-01-26 发布日期:2015-02-05
  • 通讯作者: 刘伟
  • 基金资助:

    国家自然科学基金(Nos. 81102374, 21272171, 21302139)资助项目.

Synthesis and Biological Evaluation of Phosphotyrosyl Mimetic as a Novel Protein Tyrosine Phosphatase 1B Inhibitor

Zhou Xiaoweia, Tang Yantingb, Sang Fengc, Zhang Xiulia, Li Lixinb, Zhou Honggangc, Liu Weid, Dai Yujiea   

  1. a College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457;
    b High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biotechnology and Medicine, TEDA, Tianjin 300457;
    c College of Pharmacy, Nankai University, Tianjin 300071;
    d College of Sciences, Tianjin University of Science and Technology, Tianjin 300457
  • Received:2014-12-16 Revised:2015-01-26 Published:2015-02-05
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 81102374, 21272171, 21302139).

Protein tyrosine phosphatase 1B (PTP1B) has been known to be a promising target for the treatment of type 2 diabetes and obesity. According to the reported phosphotyrosyl mimetics A, a new PTP1B inhibitor 1 was designed via computer-assisted drug design. The target compound 1 was achieved through eleven steps with Negishi cross-coupling reaction, diastereoselective sulfinylimine enolate addition reaction and the Dess-Martin oxidation as key steps. The compound 1 inhibited PTP1B competitively with an IC50 value of 54.17 μmol·L-1 in vitro.

Key words: protein tyrosine phosphatase 1B (PTP1B), phosphotyrosyl mimetics, inhibitors