6-烷胺酰肼基-1-氮杂苯并蒽酮衍生物的合成及生物活性研究  

Synthesis and Biological Evaluation of 6-[(Alkylamino)- hydrazide-yl]-1-azabenzanthrone Derivatives

作　　者：钟书明[1] 卫沈旗 刘允[1] 唐煌[1] 

机构地区：[1]f广西师范大学化学化工学院药用资源化学与药物分子工程教育部重点实验室,桂林541004

出　　处：《有机化学》2014年第1期137-146,共10页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.81260471);广西自然科学基金(No.2013GXNSFAA019038);药用资源化学与药物分子工程教育部重点实验室(No.CMEMR2012-A05)资助项目~~

摘　　要：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 novel 6-substituted 1-azabenzanthrone derivatives have been designed and synthesized from 4-chlorophenethylamine and phthalic anhydride. Their abilities to inhibit acetylcholinesterase （AChE）, butyrylcholinesterase （BChE） and AChE-induced β-amyloid （Aβ） aggregation were also tested. The synthetic compounds exhibited moderate cholinesterase inhibitory activity with IC50 values in the micromolar range in most cases. Non-competitive inhibition was found for these derivatives to AChE by the graphical analysis of steady-state inhibition data. Moreover, all compounds exhibited significant inhibitory activity on AChE-induced Aβ aggregation with inhibitory potency from 35.3% to 62.2%. Finally, eleven out of eighteen synthetic compounds were predicted to be able to cross the blood-brain barrier （BBB） to reach their targets in the central nervous system （CNS） according to a parallel artificial membrane permeation assay.

关 键 词：1-氮杂苯并蒽酮衍生物 合成 Β-淀粉样蛋白 乙酰胆碱酯酶抑制剂 血脑屏障 

分 类 号：TQ460.1[化学工程—制药化工] O621.3[理学—有机化学]