1,2,4-三唑-3-硫醚衍生物的合成、晶体结构与神经氨酸酶抑制活性  

Synthesis,Crystal Structure and Neuraminidase Inhibitory Activity of 1,2,4-Triazole-3-sulfide Derivatives

作　　者：何梅 贺超凡 刘玲 叶姣[1] 胡艾希[1] 陈云[1] 许律捷 刘艾林[2] He Mei;He Chaofan;Liu Ling;Ye Jiao;Hu Aixi;Chen Yun;Xu Lujie;Liu Ailin(College of Chemistry and Chemical Engineering,Hunan University,Changsha 410082;Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050)

机构地区：[1]湖南大学化学化工学院,长沙410082 [2]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《有机化学》2020年第8期2402-2410,共9页Chinese Journal of Organic Chemistry

基　　金：湖南省自然科学基金(No.2019JJ40030)资助项目。

摘　　要：设计并合成了一系列1,2,4-三唑-3-硫醚衍生物,目标化合物的化学结构经1H NMR、13C NMR、质谱和元素分析确证;采用单晶X射线衍射法测定了(E)-4-(4-羟基-3-甲氧基苯基亚甲氨基)-5-乙基-4H-1,2,4-三唑-3-丙硫醚(1c)的晶体结构.目标化合物体外神经氨酸酶(Neuraminidase,NA,H1N1)抑制活性测试结果表明,大部分化合物1具有较好的NA抑制活性,其中(E)-4-(4-羟基-3-甲氧基苯基亚甲氨基)-5-乙基-4H-1,2,4-三唑-3-乙硫醚(1b)和1c的NA抑制活性最佳,其IC50值分别为(6.86±2.08)和(9.1±1.56)μg/mL.A series of 1,2,4-triazole-3-sulfide derivatives were designed and synthesized.Their chemical structures were confirmed by 1H NMR,13C NMR,MS and elemental analysis.The crystal structure of(E)-4-(4-hydroxy-3-methoxyphenyl-methyleneamino)-5-ethyl-4H-1,2,4-triazole-3-propylsulfide(1c)was determined by X-ray diffraction analysis.The preliminary assay of neuraminidase(NA,H1N1)inhibitory activity in vitro showed that most of compound 1 has more potent NA inhibitory activity.Among them,compounds(E)-4-(4-hydroxy-3-methoxyphenyl-methyleneamino)-5-ethyl-4H-1,2,4-triazole-3-ethylsulfide(1b)and 1c showed the best inhibitory activity with IC50 values of(6.86±2.08)and(9.1±1.56)μg/mL,respectively.

关 键 词：1 2 4-三唑-3-硫醚衍生物 合成 晶体结构 神经氨酸酶抑制活性 

分 类 号：TQ460.1[化学工程—制药化工] O626.26[理学—有机化学]