Citation: 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 shu

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

Li Yingjun ^a,, ,
Zhao Yue ^a ,
Jin Kun ^b ,
Gao Lixin ^c ,
Sheng Li ^c ,
Liu Xuejie ^a ,
Yang Hongjing ^a ,
Lin Ledi ^a ,
Li Jia ^c,,

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

Corresponding author: Li Yingjun, chemlab.lnnu@163.com Li Jia, jli@simm.ac.cn
Received Date: 10 January 2019
Revised Date: 12 April 2019
Available Online: 16 September 2019
Fund Project: Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126)the Natural Science Foundation of Liaoning Province 20102126

Figures(8)

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