R-Flurbiprofen的制备及应用

文档编号:SW142  文档字数:10847,页数:30

摘 要：阿尔茨海默病(Alzheimer disease, AD)是临床常见疾病，阿尔茨海默病患者脑组织内β-淀粉样蛋白（Amyloidβ-protein，Aβ）明显增多，并形成大量的老年斑。老年斑、神经原纤维缠结和血管壁淀粉样变是AD大脑的特征性病理改变，而Aβ是老年斑和血管壁淀粉样变性的主要成分。现有大量的实验结果和临床资料表明，Aβ是各种原因诱发AD的共同通路，是AD形成和发展的关键因素。氟比洛芬的R-对映体可以抑制脑内γ分泌酶，阻止淀粉样蛋白前体转为β淀粉样蛋白，从而使脑内β淀粉样蛋白水平降低，因而具有很好的抑制AD发生和进一步发展的作用。同时，本品不产生非甾体抗炎药常有的胃肠道毒性。可以用以国内价格较低廉的2-氟苯胺为起始原料，经l，3-二溴-5，5-二甲基海因(DBDMH)溴代、与苯缩合成联苯、再经格氏反应与2-溴丙酸钠进行偶联，酸化后方便地得到外消旋的氟比洛芬，再经葡辛胺拆分得到而R-氟比洛芬。
关键词：阿尔茨海默病；β淀粉样蛋白；合成；R-氟比洛芬；拆分

R-Flurbiprofen Preparation and Application 
Abstract: Alzheimer's disease (AD) is a common disease. If a person suffers Alzheimer's disease, the amyloid β-protein (Aβ) within brain tissue obviously increases and forms a large number of senile plaques. Senile plaques, neurofibrillary tangles and vascular amyloidosis are characteristic pathologic changes of AD, and Aβ is the major components of senile plaques and vascular amyloidosis. A large number of experimental results and clinical data showed that Aβ is the common pathway of AD, and is the key factors of the formation and development of AD. The R-enantiomer of flurbiprofen can inhibit brain γ-secretase and prevent amyloid precursor protein turning into β-amyloid protein, so that the Aβ levels of brain decreased, and so they do good to inhibit AD occurrence and further development. Meanwhile, R- flurbiprofen does not produce gastrointestinal toxicity that a non-steroidal anti-inflammatory drug often does. 2-fluoroaniline was brominated with l,3-dibromo-5,5-dimethylhydantoin, then condensed with benzene to give 2-fluoro-4-bromo-biphenyl, which reacted with sodium 2-bromopropionate by a grlgnard coupling reaction. then split to give the goal R-Flurbiprofen.
Keywords：Alzheimer disease；Amyloid β-protein; synthesize;
R- Flurbiprofen; Resolution;

目  录
中文摘要 I
英文摘要 II
目录 III
1. 绪论 1
 1.1  氟比洛芬介绍 1
 1.2  R-氟比洛芬的研究 2
 1.3  阿尔茨海默病的介绍和发展 2
 1.4 R-氟比洛芬的作用机理 4
 1.5 R-氟比洛芬的合成过程 4
2. 实验部分 6
 2.1 仪器和试剂 6
 2.2 实验原理 6
 2.3 实验过程 11
3. 实验结果分析和讨论 13
 3.1核磁共振原理和分析  13
 3.2 实验所得核磁共振图谱分析 16
 3.3 实验过程讨论 17
4. 总结与展望 18
致谢 19
参考文献 20
附录A 22

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