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目的设计合成3-芳基-6-(溴代芳甲基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物,并探讨C-6位芳甲基上引入溴原子对其乙酰胆碱酯酶抑制活性的影响。方法以4-羟基苯甲醛为原料,经溴代反应,得到3-溴-4-羟基苯甲醛和3,5-二溴-4-羟基苯甲醛,再将溴代的4-羟基苯甲醛与乙酰甘氨酸经Erlenmeyer-Plchl反应、水解反应、缩合反应合成目标化合物3-芳基-6-(溴代芳甲基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物。采用Ellman法对目标化合物进行体外乙酰胆碱酯酶抑制活性筛选。结果所有目标化合物的结构均经红外光谱、质谱和核磁共振氢谱确证。目标化合物经体外乙酰胆碱酯酶抑制活性筛选,结果显示:所有目标化合物均具有乙酰胆碱酯酶抑制活性,其中8个化合物在10μmol.L-1浓度水平抑制活性超过了40%。结论在7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物母核C-6位芳甲基中引入溴原子的3-芳基-6-(溴代芳甲基)-7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮类化合物普遍具有较高的AChE抑制活性,并且引入2个溴原子的化合物抑制活性明显高于引入1个溴原子的化合物。
Aim To design and synthesize 3-aryl-6- (brominated arylmethyl) -7H-thiazolo [3,2-b] -1,2,4-triazin- Effect of Introducing Bromine on the Aryl Methyl Group 's Acetylcholinesterase Inhibitory Activity. Methods Starting from 4-hydroxybenzaldehyde and bromination, 3-bromo-4-hydroxybenzaldehyde and 3,5-dibromo-4-hydroxybenzaldehyde were obtained. Acetylglycine by Erlenmeyer-Plchl reaction, hydrolysis reaction and condensation reaction to synthesize the target compound 3-aryl-6- (brominated arylmethyl) -7H-thiazolo [3,2-b] -triazine-7-one compounds. Ellman's method was used to screen the target compounds for acetylcholinesterase inhibition in vitro. Results All target compounds were confirmed by IR, MS and 1H NMR. The target compounds were screened by in vitro acetylcholinesterase inhibitory activity. The results showed that all of the target compounds exhibited acetylcholinesterase inhibitory activity, of which 8 compounds had an inhibitory activity of more than 40% at a concentration of 10 μmol.L-1. Conclusion The introduction of the bromine atom of 3-aryl-6- (4-methyl-3-oxazolidinyl) Bromoarylmethyl) -7H-thiazolo [3,2-b] -1,2,4-triazin-7-one generally has a high AChE inhibitory activity, and a compound that introduces two bromine atoms Inhibitory activity was significantly higher than the introduction of a bromine atom compound.