5-氨甲基咔唑衍生物的设计、合成及抗阿尔茨海默病活性  

Design,synthesis and anti-Alzheimer's disease activity of 5-akylaminomethyl substituted carbazole derivatives

作　　者：陈萌菲 房雷[2] 陈莉[1] 

机构地区：[1]中国药科大学天然药物化学教研室,南京210009 [2]东南大学化学化工学院药物研究中心,南京210009

出　　处：《中国药科大学学报》2015年第6期647-652,共6页Journal of China Pharmaceutical University

摘　　要：以5-氨甲基咔唑为先导物,在其母环及5-位氨甲基的氮原子上引入不同的取代基,设计、合成了一系列咔唑衍生物,测试了其乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)抑制活性,以及体外神经元细胞保护活性,并总结了构效关系。其中,化合物8a具有AChE/BChE双重抑制活性,同时还能够有效保护PC12细胞免受Aβ造成的损伤,展现出良好的开发前景。A series of carbazole derivatives were designed and synthesized via the introduction of various substi uents on the carbazole template and the nitrogen atom using 5-aminomethyl substituted carbazole as the lead compound. The inhibitory activity towards AChE/BChE and the neuroprotective effect against Aβ-induced toxicity were evaluated by Ellman and MTT assay, respectively. Furthermore, the SAR of the target compounds was discussed. Among all the target compounds, compound 8a showed dual inhibitory activity toward both AChE and BChE, and could effectively protect PC12 cells from Aβ-induced toxicity, indicating compound 8a could be considered as a promising candidate against Alzheimer＇s disease.

关 键 词：咔唑衍生物 阿尔茨海默病 胆碱酯酶抑制剂 神经元保护 多功能 

分 类 号：R91[医药卫生—药学] R914.5