有机化学 ›› 2017, Vol. 37 ›› Issue (2): 485-495.DOI: 10.6023/cjoc201607030 上一篇    下一篇

研究论文

新型3,6-二取代三唑并噻二唑衍生物的合成及细胞分裂周期25B磷酸酶和蛋白酪氨酸磷酸酶1B抑制活性研究

李英俊a, 李继阳a, 彭立娜a, 高立信b, 靳焜c, 盛丽b, 张楠a, 王思远a, 李佳b   

  1. a 辽宁师范大学化学化工学院 大连 116029;
    b 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;
    c 大连理工大学精细化工国家重点实验室 大连 116012
  • 收稿日期:2016-07-20 修回日期:2016-08-30 发布日期:2016-10-08
  • 通讯作者: 李英俊, 李佳 E-mail:chemlab.lnnu@163.com
  • 基金资助:

    辽宁省自然科学基金(No.20102126)资助项目.

Synthesis and Cell Division Cycle 25B Phosphatase and Protein Ty-rosine Phosphatase 1B Inhibitory Activity Evaluation of Novel 3,6-Disubstituted Triazolothiadiazole Derivatives

Li Yingjuna, Li Jiyanga, Peng Lina, Gao Lixinb, Jin Kunc, Sheng Lib, Zhang Nana, Wang Siyuana, Li Jiab   

  1. a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
    b State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203;
    c State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012
  • Received:2016-07-20 Revised:2016-08-30 Published:2016-10-08
  • Supported by:

    Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).

以邻苯二胺和一氯乙酸为初始原料,经多步反应,合成了一系列新型含苯并咪唑环和芳磺酰基的3,6-二取代三唑并噻二唑衍生物7a~7y.利用1H NMR、IR和元素分析对新的中间体化合物3、4、6及目标产物7进行了结构表征.对所合成的目标化合物进行了细胞分裂周期25B磷酸酶(Cdc25B)和蛋白酪氨酸磷酸酶1B(PTP1B)抑制活性筛选,实验结果显示,部分目标化合物对Cdc25B和PTP1B显示出良好的抑制活性,其中目标化合物7d对Cdc25B的抑制活性最高[IC50=(7.72±0.73)μg/mL],7u对PTP1B的抑制活性最高[IC50=(3.31±0.57)μg/mL].值得注意的是,化合物7b、7d、7l、7t7u对Cdc25B和PTP1B均具有抑制活性.这些活性的目标化合物是潜在的Cdc25B和PTP1B抑制剂,在癌症和糖尿病治疗方面具有很好的应用前景.

关键词: 三唑并噻二唑, 苯并咪唑, 芳磺酰基, 合成, Cdc25B和PTP1B抑制剂

A series of new 3,6-disubstituted triazolothiadiazole derivatives 7a~7y containing benzimidazole and arylsulfonyl moities have been synthesized by o-phenylenediamine and chloroacetic acid as starting materials via multistep reactions.The structures of the intermediates 3,4,6 and the target compounds 7 were characterized by 1H NMR,IR spectra and elemental analysis.All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25B phosphatase (Cdc25B) and protein tyrosine phosphatase 1B (PTP1B).The results show that some of them display significant inhibitory activities against Cdc25B and PTP1B.Among them,compound 7d exhibits the highest inhibitory activity against Cdc25B [IC50=(7.72±0.73)μg/mL]and 7u exhibits the highest inhibitory activity against PTP1B[IC50=(3.31±0.57)μg/mL].It is noteworthy that compounds 7b,7d,7l,7t and 7u show higher inhibitory activities against Cdc25B and PTP1B.They can be considered as potential Cdc25B and PTP1B inhibitors,and have great application prospects in the treatment of cancers and diabetes.

Key words: triazolothiadiazole, benzimidazole, arylsulfonyl, synthesis, Cdc25B and PTP1B inhibitors