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  

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

作　　者：李英俊[1] 杨鸿境 曹欣[1] 高立信 靳焜[3] 盛丽 刘季红[4] 刘雪洁 李佳 LI Yingjun;YANG Hongjing;CAO Xin;GAO Lixin;JIN Kun;SHENG Li;LIU Jihong;LIU Xuejie;LI Jia(College of Chemistry and Chemical Engineering,Liaoning Normal University,Dalian,Liaoning 116029,China;National Center for Drug Screening,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;State Key Laboratory of Fine Chemicals,Dalian University of Technology,Dalian,Liaoning 116012,China;Chemistry Analysis and Inspection Center,Dalian University of Technology,Dalian,Liaoning 116023,China)

机构地区：[1]辽宁师范大学化学化工学院,辽宁大连116029 [2]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 [3]大连理工大学精细化工国家重点实验室,辽宁大连116012 [4]大连理工大学化学分析测试中心,辽宁大连116023

出　　处：《应用化学》2020年第9期994-1002,共9页Chinese Journal of Applied Chemistry

基　　金：辽宁省自然科学基金(20102126)项目资助。

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(IC 50)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。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(IC 50)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.

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 

分 类 号：O626[理学—有机化学]