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Chinese Journal of Organic Chemistry >

2019 , Vol. 39 >Issue 9: 2599 - 2608

DOI: https://doi.org/10.6023/cjoc201901013

ARTICLE

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

  • Li Yingjun ,
  • Zhao Yue ,
  • Jin Kun ,
  • Gao Lixin ,
  • Sheng Li ,
  • Liu Xuejie ,
  • Yang Hongjing ,
  • Lin Ledi ,
  • Li Jia
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  • 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 date: 2019-01-10

  Revised date: 2019-04-12

  Online published: 2019-04-16

Supported by

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

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Abstract

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

Cite this article

Li Yingjun , Zhao Yue , Jin Kun , Gao Lixin , Sheng Li , Liu Xuejie , Yang Hongjing , Lin Ledi , Li Jia . Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity[J]. Chinese Journal of Organic Chemistry, 2019 , 39(9) : 2599 -2608 . DOI: 10.6023/cjoc201901013

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