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目的寻找作为乙酰胆碱酯酶抑制剂的具有新化学结构类型的化合物。方法采用分子对接的方法寻找新型的乙酰胆碱酯酶抑制剂,设计并合成了10个7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物。通过Erlenmeyer-Pl chl反应及缩合反应生成目标化合物6-芳甲基-3-芳基-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物,其结构经红外光谱、质谱和核磁共振氢谱确证。采用Ellman方法进行体外抑制乙酰胆碱酯酶活性测试。结果合成了10个7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物,体外抑制乙酰胆碱酯酶活性测试结果显示所有目标化合物均具有抑制乙酰胆碱酯酶活性,8个目标化合物在10μmo.lL-1浓度水平抑制活性均超过了50%。结论7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物是潜在的乙酰胆碱酯酶抑制剂,是一类具有新骨架结构的AChE抑制剂。
Aim To find compounds with a new chemical structure as acetylcholinesterase inhibitors. Methods A novel acetylcholinesterase inhibitor was identified by molecular docking. Ten 7H-thiazolo [3,2-b] -1,2,4-triazin-7-one compounds were designed and synthesized. The target compound 6-arylmethyl-3-aryl-7H-thiazolo [3,2-b] -1,2,4-triazin-7-one was obtained by Erlenmeyer-Pl reaction and condensation reaction. Its structure was confirmed by IR, MS and 1H-NMR. In vitro inhibition of acetylcholinesterase activity using the Ellman method. Results Ten 7H-thiazolo [3,2-b] -1,2,4-triazin-7-one compounds were synthesized and their inhibitory activity on acetylcholinesterase was tested in vitro. All of the target compounds showed inhibitory activity against acetylcholinesterase Activity, the inhibitory activity of 8 target compounds exceeded 50% at the concentration of 10 μmol·L-1. Conclusion 7H-thiazolo [3,2-b] -1,2,4-triazin-7-ones are potential acetylcholinesterase inhibitors and are a class of AChE inhibitors with novel scaffolds.