2H-噻唑[3,2-b][1,2,4]三嗪-3,7-二酮类化合物的设计、合成及生物活性  

Design, synthesis and biological activity of 2H-thiazole[3,2-b][1,2,4]triazine-3,7-diones

作　　者：刘斯婕[1] 赵星[1] 何敬宇[1] 高佳丽 王娟[1] LIU Sijie;ZHAO Xing;HE Jingyu;GAO Jiali;WANG Juan(College of Chemical Engineering,Shijiazhuang University,Shijiazhuang 050035,Hebei,China)

机构地区：[1]石家庄学院化工学院,河北石家庄050035

出　　处：《精细化工》2021年第6期1199-1203,1211,共6页Fine Chemicals

基　　金：河北省自然科学基金青年基金(H2018106015);河北省三三三人才培养资助项目(A201803051)。

摘　　要：为寻找高活性的乙酰胆碱酯酶(ACh E)抑制剂,以取代的苯甲醛和N-乙酰甘氨酸为原料经过5步反应合成了13个2H-噻唑[3,2-b][1,2,4]三嗪-3,7-二酮类化合物。目标化合物结构经1HNMR,13CNMR和HRMS确认,采用Ellman法测试了化合物在浓度10μmol/L下对ACh E的抑制活性。结果显示,所有目标化合物均具有抑制活性,其中,化合物6-(4-甲氧基苄基)-2-(4-甲氧基苯亚甲基)-2H-噻唑并[3,2-b]-1,2,4-三嗪-3,7-二酮(Ⅴk)活性最好,抑制率达到80.1%±3.1%。通过分子对接研究了化合物Ⅴk和AChE的结合模式,Ⅴk可以跟AChE的多个催化位点结合。In order to search for high activity acetylcholinesterase(AChE) inhibitors, thirteen 2H-thiazole[3,2-b][1,2,4]triazine-3,7-diones were synthesized from substituted benzaldehyde and N-acetylglycine through five steps. The structures of the target compounds were confirmed by 1HNMR, 13CNMR and HRMS. Ellman method was used to test AChE inhibitory activity of the compounds at 10 μmol/L. The results showed that all the target compounds had inhibitory activity against AChE, and the compound 6-(4-methoxybenzyl)-2-(4-methoxybenzylidene)-2 H-thiazolo[3,2-b]-1,2,4-triazine-3,7-dione(Ⅴk) had the best activity with an inhibition rate of 80.1%±3.1%. The binding mode of compound Ⅴk and AChE was studied by molecular docking. Compound Ⅴk could bind to multiple catalysis sites of AChE.

关 键 词：2H-噻唑[3 2-b][1 2 4]三嗪-3 7-二酮 合成 活性 对接 乙酰胆碱酯酶抑制剂 医药原料 

分 类 号：R914.5[医药卫生—药物化学]