四氢异喹啉类单胺氧化酶抑制剂的合成及其活性研究  

Study on synthesis of tetrahydroisoquinolines and monoamine oxidase inhibitory activity

作　　者：曾庆东[1] 张万萍[1] 程鹏[1] 李文军[1] 鲁振浩[1] 彭杨[1] 朱必敏[1] 余瑜[1] 

机构地区：[1]重庆医科大学药学院药物化学教研室,重庆400016

出　　处：《重庆医科大学学报》2013年第6期574-576,共3页Journal of Chongqing Medical University

基　　金：国家科技重大专项课题"重大新药创制"资助项目(编号:2010ZX09401-306-1-1)

摘　　要：目的:设计合成含1,2,3,4-四氢异喹啉结构的单胺氧化酶(monoamine oxidase,MAO)抑制剂,并考察其活性。方法:以苯乙胺为原料,经酰化、氨基化、环合和肼解还原反应制得中间体1-氨甲基-1,2,3,4-四氢异喹啉,再衍生化制得目标化合物,并进行MAO的抑制作用研究。结果:合成了新型四氢异喹啉类MAO抑制剂5个,其中新化合物(5,6,7,9)的结构经质谱、红外光谱及氢谱核磁共振分析确证。经体外MAO抑制实验结果显示,5个目标化合物都具有一定的MAO抑制作用,其中化合物5、6、7对MAO-A有较好的选择性抑制作用。结论:设计合成的目标化合物5、6、7具有进一步深入研究的实用价值。Objective：To design and synthesize 1,2,3,4-tetrahydroisoquinolines and to determine its inhibition effect on monoamine oxidase （MAO）. Methods： 1 -aminomethyl-1,2,3,4-tetrahydroisoquinoline was synthesized from phenylethylamine via acylation, ami-nation with phthalimide potassium, bisehler-napieralski cyclization, hydrazinolysis and reduction reaction. Then the title compounds were synthesizeda？esults：Four compounds with tetrahydroisoquinoline moiety were synthesized and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry. Pharmacological test in vitro showed that all the five compounds had certain MAO inhibitory activity,and compound（5-7） displayed preferable selective inhibition on MAO-A. Conclusion ：The obtained compounds（5-7） need further study.

关 键 词：四氢异喹啉 环合 肼解 还原 单胺氧化酶 抑制剂 

分 类 号：R914[医药卫生—药物化学]