新型[1,3]二氧杂环戊烯并[4,5-f]异吲哚酮衍生物的设计、合成与活性研究  

Design, synthesis and biological evaluation of novel [1,3]dioxolo[4,5-f]isoindolone derivatives

作　　者：龚永祥 朱齐凤 钟金清 刘礼飞 李旭飞 郑晓鹤 骆红英 赵旭阳 

机构地区：[1]浙江海正药业股份有限公司,浙江台州318000

出　　处：《药学学报》2015年第2期191-198,共8页Acta Pharmaceutica Sinica

摘　　要：本文设计、合成了一系列新型[1,3]二氧杂环戊烯并[4,5-f]异吲哚酮衍生物,并对其进行了乙酰胆碱酯酶抑制活性以及由东莨菪碱致小鼠记忆障碍的改善作用测试。实验结果表明目标化合物对乙酰胆碱酯酶（ACh E）均有抑制作用,IC50值在微摩尔级,其中化合物I1（IC50=0.086μmol·L-1）和I2（IC50=0.080μmol·L-1）对ACh E的抑制活性较好,与阳性药多奈哌齐（IC50=0.094μmol·L-1）相当;且化合物I1~I4均具有改善由东莨菪碱引起的小鼠记忆障碍的作用。A series of [1,3]dioxolo[4,5-f]isoindolone derivatives were designed, synthesized and evaluated as inhibitors of acetylcholinesterases（ACh E）. Furthermore, their effects on memory impairment of mice induced by scopolamine were investigated with step-through test. The results suggested that most of the target compounds exhibited potential inhibition on ACh E with IC50 values at micromolar range. Compounds I1（IC50value of 0.086 μmol·L-1） and I2（IC50 value of 0.080 μmol·L-1） showed the strongest ACh E inhibitory activity, which are equipotent to donepezil（IC50 value of 0.094 μmol·L-1）. Moreover, compounds I1-I4 could improve the memory impairment induced by scopolamine in mice.

关 键 词：[1 3]二氧杂环戊烯并[4 5-f]异吲哚酮 乙酰胆碱酯酶抑制剂 记忆障碍 阿尔茨海默症 

分 类 号：R916[医药卫生—药学]