Citation: LI Yingjun, YANG Hongjing, CAO Xin, GAO Lixin, JIN Kun, SHENG Li, LIU Jihong, LIU Xuejie, LI Jia. Synthesis of 3, 6-Disubstituted Triazolothiadiazole Derivatives and Their Inhibitory Activities Against Cell Division Cycle 25B Phosphatase and Protein Tyrosine Phosphatase 1B[J]. Chinese Journal of Applied Chemistry, ;2020, 37(9): 994-1002. doi: 10.11944/j.issn.1000-0518.2020.09.200040 shu

Synthesis of 3, 6-Disubstituted Triazolothiadiazole Derivatives and Their Inhibitory Activities Against Cell Division Cycle 25B Phosphatase and Protein Tyrosine Phosphatase 1B

LI Yingjun ^a,, ,
YANG Hongjing ^a ,
CAO Xin ^a ,
GAO Lixin ^b ,
JIN Kun ^c ,
SHENG Li ^b ,
LIU Jihong ^d ,
LIU Xuejie ^a ,
LI Jia ^b,,

a.
College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, Liaoning 116029, China
b.
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
c.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, Liaoning 116012, China
d.
Chemistry Analysis and Inspection Center, Dalian University of Technology, Dalian, Liaoning 116023, China

Corresponding author: LI Yingjun, chemlab.lnnu@163.com LI Jia, jli@simm.ac.cn
Received Date: 16 February 2020
Revised Date: 13 April 2020
Accepted Date: 5 June 2020

Fund Project: Natural Science Foundation of Liaoning Province No.20102126Supported by the Natural Science Foundation of Liaoning Province(No.20102126)

Figures(2)

A series of 3, 6-disubstituted triazolothiadiazole derivatives 3a-3l containing benzimidazole/aryloxymethyl scaffolds was synthesized. Their structures were confirmed by Fourier transform infrared spectrometry (FT-IR), nuclear magnetic resonance spectroscopy (NMR) and elemental analysis. The inhibitory activity of all synthesized target compounds against cell division cycle 25B phosphatase (Cdc25B)/protein tyrosine phosphatase 1B (PTP1B) was evaluated, and the structure-activity relationship was discussed. The bioassay results show that target compound 3a has the highest inhibitory activity against Cdc25B and PTP1B with the half inhibitory concentration (IC₅₀) values of (0.46±0.02) μg/mL and (1.77±0.40) μg/mL, respectively. The obtained research results provide a reference for the development of novel Cdc25B/PTP1B inhibitors.
- triazolothiadiazole,
- benzimidazole,
- aryloxyacetic acid,
- cell division cycle 25B phosphatase inhibitor,
- protein tyrosine phosphatase 1B inhibitor
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