双5-苄基-1,3,4-噁二唑衍生物的合成,晶体结构和乙酰胆碱酯酶抑制活性研究  

Synthesis,crystal structure and acetylcholinesterase-inhibition activities of bis 5-benzyl-1,3,4-oxadiazole derivatives

作　　者：杨顺 武文龙 邹靖培 钱晶晶 刘玉委 尹福军 史大华 YANG Shun;WU Wen-long;ZOU Jing-pei;QIAN Jing-jing;LIU Yu-wei;YIN Fu-jun;SHI Da-hua(School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China)

机构地区：[1]江苏海洋大学药学院,江苏连云港222005

出　　处：《化学研究与应用》2022年第5期1083-1090,共8页Chemical Research and Application

基　　金：江苏省自然科学基金项目(BK20191470)资助;江苏高校优势学科建设工程项目(PAPD);江苏省研究生科研与实践创新项目(KYCX20-2895)。

摘　　要：以4-甲氧基苯乙酸为原料,经过多步反应合成得到3个5-苄基-1,3,4-噁二唑衍生物(5a-5c)。产物结构经^(1)H NMR、^(13)C NMR和X-单晶衍射进行表征。采用Ellma法分析检测化合物5a-5c的乙酰胆碱酯酶抑制活性。结果表明化合物5a与5b具有显著的乙酰胆碱酯酶抑制活性,其中化合物5b乙酰胆碱酯酶抑制活性最高,该化合物抑制乙酰胆碱酯酶的IC_(50)值为:1.04μM。化合物的5b的晶体结构显示该化合物是一个对称分子,属于单斜晶系,P2_(1)/c空间群。分子对接显示,5b能够与乙酰胆碱酯酶的PAS位点和CAS位点相结合,是一种双结合位点的乙酰胆碱酯酶抑制剂。Three bis-5-benzyl^(-1),3,4-oxadiazole derivatives(5a-5c)were synthesized from 4-methoxyphenylacetic acid.The structure was characterized by^(1)H NMR,^(13)C NMR and X-single crystal diffraction.The acetylcholinesterase inhibitory activity of compounds 5a-5c was analyzed by Ellma method.The results showed that compounds 5a and 5b had significant acetylcholinesterase inhibitory activity,and compound 5b had the highest acetylcholinesterase inhibitory activity.The IC_(50) value of the compound for inhibiting acetylcholinesterase is 1.04μM.The crystal structure of 5b shows that the compound is a symmetrical molecule,belonging to monoclinic system and P2_(1)/c space group.Molecular docking showed that compound 5b could interact with PAS site and CAS of acetylcholinesterase as a dual binding site inhibitors of acetylcholinesterase.

关 键 词：1 3 4-噁二唑 晶体结构 乙酰胆碱酯酶 阿尔茨海默症 

分 类 号：O741.6[理学—晶体学]