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

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.