新型含咔唑环芳氨基乙酰腙衍生物的合成及其蛋白酪氨酸磷酸酶1B(PTP1B)抑制活性评价  

Synthesis and Protein Tyrosine Phosphatase 1B(PTP1B)Inhibitory Activity Evaluation of Novel Arylaminoacetylhydrazone Derivatives Containing Carbazole Moiety

作　　者：李英俊[1] 林乐弟 靳焜[2] 高立信 盛丽 刘季红[4] 李佳 Li Yingjun;Lin Ledi;Jin Kun;Gao Lixin;Sheng Li;Liu Jihong;Li Jia(College of Chemistry and Chemical Engineerings Liaoning Normal University,Dalian,Liaoning 116029;State Key Laboratory of Fine Chemicals,Dalian University of Technology,Dalian,Liaoning 116012;State Key Laboratory of Drug Research,National Center for Drug Screening,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203;Chemistry Analysis and Inspection Center,Dalian University of Technology,Dalian,Liaoning 116023)

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

出　　处：《有机化学》2021年第8期3157-3170,共14页Chinese Journal of Organic Chemistry

基　　金：辽宁省自然科学基金(No.20102126)资助项目.

摘　　要：为寻找新型蛋白酪氨酸磷酸酶1B(PTP1B)抑制剂,设计并合成了一系列新型含咔唑环芳氨基乙酰腙衍生物.其结构和构型用IR、^(1)H NMR、^(13)C NMR和2D NMR(包括^(1)H-^(1)H COSY、^(1)H-^(13)C HMBC和NOESY)谱及元素分析进行了确证.通过对PTP1B抑制活性的测试发现,目标化合物对PTP1B有较强的抑制作用,且大多数化合物的IC_(50)值低于阳性对照药物齐墩果酸,其中N'-(9-辛基咔唑-3-亚甲基)-2-(4-硝基苯氨基)乙酰肼(3t)活性最高,IC_(50)=(2.78±0.04)μmol/L.利用分子对接研究了化合物3t与PTP1B酶的结合情况.In order to find novel protein tyrosine phosphatase 1B(PTP1B)inhibitors,a series of novel arylaminoacetylhydra-zone derivatives containing carbazole moiety were designed and synthesized.Their structures and configurations were confirmed by IR,^(1)H NMR,^(13)C NMR,two-dimensional NMR spectra(including^(1)H-^(1)H COSY,^(1)H-^(13)C HMBC and NOESY)and elemental analysis.The inhibitory activities of all the target compounds against PTP1B were tested,and it was found that the target compounds had potent inhibitory activity against PTP1B,and most of them had lower IC_(50) value than the positive con-trol drug oleanolic acid.Among them,N'-(9-octylcarbazol-3-ylmethylene)-2-(4-nitrophenylamino)acetohydrazide(3t)had the highest inhibitory activity against PTP1B with IC_(50) of(2.78±0.04)μmol/L.Molecular docking was used to study the bind of compound 3t with PTP1B enzyme.

关 键 词：蛋白酪氨酸磷酸酶1B(PTP1B)抑制剂 咔唑 芳氨基乙酰腙 合成 分子对接 

分 类 号：TQ464.8[化学工程—制药化工]