Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (9): 2599-2608.DOI: 10.6023/cjoc201901013 Previous Articles     Next Articles



李英俊a, 赵月a, 靳焜b, 高立信c, 盛丽c, 刘雪洁a, 杨鸿境a, 林乐弟a, 李佳c   

  1. a 辽宁师范大学化学化工学院 大连 116029;
    b 大连理工大学精细化工国家重点实验室 大连 116012;
    c 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
  • 收稿日期:2019-01-10 修回日期:2019-04-12 发布日期:2019-04-16
  • 通讯作者: 李英俊, 李佳;
  • 基金资助:


Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity

Li Yingjuna, Zhao Yuea, Jin Kunb, Gao Lixinc, Sheng Lic, Liu Xuejiea, Yang Hongjinga, Lin Ledia, Li Jiac   

  1. a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
    b State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012;
    c National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
  • Received:2019-01-10 Revised:2019-04-12 Published:2019-04-16
  • Contact: 10.6023/cjoc201901013;
  • Supported by:

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

A series of novel 2,5-disubstituted-1,3,4-thiadiazolamide derivatives containing carbazole/benzimidazole moity were synthesized. Their structures were characterized by IR, 1H NMR, 13C NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and T-cell protein tyrosine phosphatase (TCPTP). The structure-activity relationship was discussed. The results showed that most of compounds had good inhibitory activity against PTP1B over the highly homologous TCPTP, and 2-(9-carbazolylmethylene)-5-(3-chlorobenzoylamino)-1,3,4-thiadiazole (5c) displayed the highest inhibitory activity against PTP1B[IC50=(2.43±0.43) μg/mL]. The inhibitory activities of 2-(9-carbazolylmethylene)-5-(4-methylbenzoylamino)-1,3,4-thiadiazole (5b) and 5c against PTP1B were higher than that of positive control oleanolic acid. Molecular docking and density functional theory (DFT) calculations of the target compound 5c were performed. The docking result showed that compound 5c and PTP1B enzyme formed a stable complex by hydrogen bonds, hydrophobic and π-π interactions.

Key words: 1,3,4-thiadiazolamide, carbazole, benzimidazole, synthesis, PTP1B inhibitor, molecular docking, density functional theory (DFT) study