Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (8): 3097-3105.DOI: 10.6023/cjoc202104041 Previous Articles     Next Articles


5-苯基-1,3,4-噻二唑衍生物的合成及含SH2结构域蛋白酪氨酸磷酸酶1 (SHP1)抑制活性研究

于丽杰a, 冯勃b,c, 王智佳a, 高立信a,b, 张纯a,d, Rajendran Satheeshkumara, 李佳b, 周宇波b,c,*(), 王文龙a,*()   

  1. a 江南大学药学院 江苏无锡 214122
    b 中国科学院上海药物研究所 国家新药筛选中心 上海 201203
    c 中国科学院药物创新研究院中山研究院 广东中山 528400
    d 南京大学化学化工学院 南京 210023
  • 收稿日期:2021-04-18 修回日期:2021-05-19 发布日期:2021-06-02
  • 通讯作者: 周宇波, 王文龙
  • 作者简介:
    † 共同第一作者
  • 基金资助:
    国家自然科学基金(21772068); 国家自然科学基金(81773779); 江苏省研究生科研与实践创新计划(KYCX20-1965); 江苏省自然科学基金(BK20190608)

Synthesis of 5-Phenyl-1,3,4-thiadiazole Derivatives and Their Biochemical Evaluation against Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 1 (SHP1)

Lijie Yua, Bo Fengb,c, Zhijia Wanga, Lixin Gaoa,b, Chun Zhanga,d, Rajendran Satheeshkumara, Jia Lib, Yubo Zhoub,c(), Wenlong Wanga()   

  1. a School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122
    b National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
    c Zhongshan Institute for Drug Discovery, Institutes of Drug Discovery and Development, Chinese Academy of Sciences, Zhongshan, Guangdong 528400
    d School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023
  • Received:2021-04-18 Revised:2021-05-19 Published:2021-06-02
  • Contact: Yubo Zhou, Wenlong Wang
  • About author:
    † (These authors contributed equally to this work).
  • Supported by:
    National Natural Science Foundation of China(21772068); National Natural Science Foundation of China(81773779); Postgraduate Research & Practice Innovation Program of Jiangsu Province(KYCX20-1965); Natural Science Foundation of Jiangsu Province(BK20190608)

The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in cancer treatment. Meanwhile only countable SHP1 inhibitors have been reported. A new type of SHP1 inhibitors with 5-phenyl-1,3,4-thiadiazole scaffold was developed. The representative compound 5b exhibited SHP1 inhibitory activity with IC50 of (1.33±0.16) μmol/L, exhibited about 2-fold selectivity for SHP1 over SHP2, and had no detectable activity against PTP1B and TCPTP, and offered a novel scaffold to develop new SHP1 inhibitors.

Key words: 5-phenyl-1,3,4-thiadiazole derivatives, Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1), inhibitors, structure-activity relationships