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以对氯苯乙胺和邻苯二甲酸酐为原料,设计合成了一系列新的6位取代的1-氮杂苯并蒽酮衍生物.并对所合成衍生物的抑制乙酰胆碱酯酶、丁酰胆碱酯酶和乙酰胆碱酯酶诱导的Aβ聚集活性进行了评价.合成的衍生物表现出中等的胆碱酯酶抑制活性,大部分化合物的抑制IC50值处于微摩尔浓度水平.动力学研究表明,衍生物对乙酰胆碱酯酶的抑制类型属于非竞争性抑制.所有化合物表现出有意义的乙酰胆碱酯酶诱导的Aβ聚集抑制活性,其抑制率在35.2%~62.2%之间.而且,合成的18个新衍生物中有11个化合物能够透过血脑屏障进入中枢神经系统.
A series of new 6-substituted 1-azabenzotetraone derivatives were designed and synthesized by using p-chlorophenethylamine and phthalic anhydride as raw materials.The inhibitory effect of the synthesized derivatives on acetylcholinesterase, Acetylcholinesterase and acetylcholinesterase-induced Aβ aggregation activity were evaluated.The synthetic derivatives showed moderate cholinesterase inhibitory activity, most of the compounds inhibit the IC50 value at micromolar levels.Kinetic studies have shown that , The type of inhibition of acetylcholinesterase by the derivatives belongs to the noncompetitive inhibition.All compounds showed significant AchE inhibitory activity induced by acetylcholinesterase and the inhibitory rate was between 35.2% -62.2% Eleven new derivatives are able to penetrate the central nervous system through the blood-brain barrier.