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阿尔茨海默病(Alzheimer’s disease,AD)是一种隐匿发病的神经系统退行性疾病。本文对已报道的具有较好乙酰胆碱酯酶抑制活性的化合物I进行结构优化,设计新的活性化合物。以乙酰基吡啶为原料,经5步反应设计合成了新的化合物,并采用Ellman分光光度法对它们的体外乙酰胆碱酯酶抑制活性进行了测试。活性测试结果表明:大部分新化合物有一定的体外乙酰胆碱酯酶抑制活性,其中化合物13c的活性最好,其IC50达到了0.15μmol·L-1,优于对照药物利斯的明和化合物I;同时,它对丁酰胆碱酯酶几乎无抑制作用,表现出较好的选择性。此类化合物可选择性抑制乙酰胆碱酯酶活性,具有进一步研究价值。
Alzheimer’s disease (AD) is an occult onset of neurodegenerative disease. In this paper, I have been reported that compounds with better inhibitory activity of acetylcholinesterase structural optimization, the design of new active compounds. Acetylpyridine was used as a starting material to synthesize new compounds through five steps and their in vitro acetylcholinesterase inhibitory activity was tested by Ellman spectrophotometry. The results of the activity test showed that most of the new compounds had some inhibitory activity on acetylcholinesterase in vitro. Among them, compound 13c had the best IC50 of 0.15μmol·L-1, which was better than that of the control drug Lees and Compound I , It has almost no inhibition of butyrylcholinesterase, showing better selectivity. Such compounds can selectively inhibit acetylcholinesterase activity, with further research value.