dimebon合成路线的改进研究

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1、贵阳医学院2012届硕士研究生毕业论文《中国图书资料分类号》单位代码：10660分类号：R914学号：S090136贵阳医学院2012届硕士学位论文Dimebon合成路线的改进研究保密：2012年5月31日至21014年5月31日研究生：张毅导师：王颖副教授汤磊教授年级：2009级专业：药剂学2012年5月22日贵阳医学院2012届硕士研究生毕业论文目录摘要··············································································

2、······································1第一章：阿尔茨海默病概述···············································2第二章：Dimebon合成路线简介·······························8第三章：实验部分···········································································18第四章：合成工艺的优化··············

3、······································25第五章：结果与讨论···································································30参考文献······································································································35致谢······························

4、··················································································39英文摘要········································································································40缩略语词表···························································

5、·····································41论文独创性声明·················································································42附：综述·································································································43贵阳医学院2012届硕士研究生毕业论文Dimebon

6、合成路线的改进研究专业：药剂学研究生：张毅导师：汤磊教授王颖副教授摘要：阿尔茨海默病是一种进行性发展的致死性神经退行性疾病，以缓慢进展的痴呆为主要表现。Medivition公司的一项研究发现Dimebon可轻度抑制丁酰胆碱酯酶和乙酰胆碱酯酶，弱阻断N-甲基-D-天冬氨酸受体信号通路，抑制线粒体通透性转运孔的开放。这些研究提示Dimebon可能作为治疗阿尔茨海默病的一种新型药物。因此，研究Dimebon的合成工艺，建立了一条适合工业化生产的合成路线，将会产生良好的经济效益。本论文以对甲苯胺与6-甲基烟酸甲酯为起始

7、原料，经重氮化、还原、酸水解、Fischer吲哚环合以及酯缩合、脱羧、羰基还原、卤代、消除反应反应分别得到2，3，4，5-四氢-2，8-二甲基-1H-吡啶（4,3-b）吲哚和2-甲基-5-乙烯基吡啶这两个关键中间体，最后在氢化钠条件下经加成反应得到目标产物Dimebon，收率为75.1%，目标产物经波谱分析与文献数据相吻合。本论文所设计合成路线操作简单、收率稳定、成本低廉，容易实现工业化生产。关键词：阿尔茨海默病，Dimebon，合成，生产工艺。第1页共62页贵阳医学院2012届硕士研究生毕业论文第一章：阿尔茨

8、海默病概述1.1阿尔茨海默病概述：1910年，德国神经病理学家阿尔茨海默（AloisAlzheimer）首次对一例具有进行性痴呆表现的患者死后病理检查时发现了该病，于是把这种病命名为阿尔茨海默病（Alzhemei’sdisease,英文简写为：AD）。阿尔茨海默病以细胞外老年斑及细胞内tau蛋白过度磷酸化导致的神经原纤维缠结形成为病理学特征，并且伴有大脑皮层神经元和轴突的丢失，是一种进