新型乙酰胆碱酯酶抑制剂7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物的设计、合成与生物活性

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-Plöchl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，其结构采用红外光谱、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10 μmol.L-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。

Design, synthesis, and biological activity of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as a new type of acetylcholinesterase inhibitors

Aim To discover new chemical structures as acetylcholinesterase inhibitors. Methods Our work is focused on finding hits with molecular docking, leading to the finding and designing of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as new AChE inhibitors. The target compounds were synthesized with Erlenmeyer-Plöchl reaction and Hantzsch-type condensation and were characterized with IR, MS and 1H-NMR. The bioactivity of the target compounds were assayed with the Ellman’s method. Results Ten target compounds were synthesized, and all showed medium inhibitory potency against human AChE in vitro, eight of them with the inhibitory rates above 50% at 10 μmol.L-1. Conclusion 7H-Thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were found to be a novel series of acetylcholinesterase inhibitors with new scaffold.