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

doi:10.11944/j.issn.1000-0518.2020.09.200040

摘要/Abstract

摘要： 合成出了一系列含苯并咪唑/芳氧甲基骨架的3,6-二取代三唑并噻二唑衍生物3a~3l,其结构经傅里叶变换红外光谱仪(FT-IR)、核磁共振波谱仪(NMR)和元素分析得以确认。评价了它们对细胞分裂周期25B磷酸酶(Cdc25B)/蛋白酪氨酸磷酸酶1B(PTP1B)的抑制活性,讨论了构效关系。生物活性测试结果显示,化合物3a对Cdc25B和PTP1B的抑制活性最高,其半数抑制浓度(IC₅₀)值分别为(0.46±0.02) μg/mL和(1.77±0.40) μg/mL。所得研究结果为开发新型Cdc25B/PTP1B抑制剂提供了参考依据。

关键词: 三唑并噻二唑, 苯并咪唑, 芳氧乙酸, 细胞分裂周期25B磷酸酶抑制剂, 蛋白酪氨酸磷酸酶1B抑制剂

Abstract: 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.

Key words: triazolothiadiazole, benzimidazole, aryloxyacetic acid, cell division cycle 25B phosphatase inhibitor, protein tyrosine phosphatase 1B inhibitor

李英俊, 杨鸿境, 曹欣, 高立信, 靳焜, 盛丽, 刘季红, 刘雪洁, 李佳. 3,6-二取代三唑并噻二唑衍生物的合成及其对细胞分裂周期25B磷酸酶和蛋白酪氨酸磷酸酶1B抑制活性评价[J]. 应用化学, 2020, 37(9): 994-1002.

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.

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