基于甲硫基乙酰胺的奈帕芬胺合成

论文编号:HG114  论文字数:9797,页数:25

 摘  要：非甾体抗炎药（NSAIDS）具有抗炎、抗过敏和止痛作用，且无皮质类固醇的不良反应，因此，其在眼科的应用日益受到重视。但是常用的几种非甾体抗炎药在使用过程中伴随着一定的副作用。为了减少不良反应的发生，寻求安全、有效的抗炎药物，近年来国内外学者对非甾体抗炎药的眼部应用进行了深入的研究，认为对其进行结构改造或制成前体药物是减少不良反应的有效途径。
 奈帕芬胺是新一代的非甾体类抗炎药，主要用于治疗白内障手术相关性疼痛和炎症。经眼部给药后，可迅速穿过角膜，并在眼组织水解酶的作用下转化为氨芬酸，它能迅速到达靶位点发挥作用。本次论文的主要工作是基于甲硫基乙酰胺来合成奈帕芬胺，并在此基础上做工艺放大试验，研究其工艺放大过程中遇到的问题难点。经过多次的实验研究，我们发现：在次氯酸叔丁酯合成过程中，避光环境下，用液氮控温至零度，反应时间为5min时有最高产率；甲硫基乙酰胺的合成过程中，氯乙酰胺的滴加时间为20min时可以有效防止暴沸；奈帕芬胺的合成过程中，次氯酸叔丁酯的滴加时间为30min时有最高产率。
 关键词：奈帕芬胺；非甾体抗炎药；甲硫基乙酰胺；

Based on methylthio acetamide for synthesis of Nepafenac

Abstract: Non-steroidal anti-inflammatory drugs (NSAIDS) anti-inflammatory, allergy and pain, and no steroids adverse reactions, therefore, its application in the eye of the growing importance. But several non-steroidal anti-inflammatory drug in use process with certain side-effects. In order to reduce adverse reaction, and seek safety and effective anti-inflammatory drugs, in recent years, domestic and foreign scholars of non-steroidal anti-inflammatory drug eye application research, think of its structure reform or precursor drug is the effective way to reduce adverse reactions.
Nepafenac is a new generation of nonsteroidal anti-inflammatory drugs used to treat cataract surgery, mainly between pain and inflammation. In the eye, drug can quickly through the cornea, and in the eyes of the hydrolysis enzyme organization under into fenway ammonia acid, it can quickly reach sites. This paper main job is to Nepafenac synthesis by methylthio acetamide, and on this basis, the scale expansion in the problems in the course of difficulty. After many experimental study，we found that in hypochlorite tert-butyl diazoacetate synthetic process，the most prolific rate is: to avoid light environment, use liquid temperature control to zero, the reaction time for 5 minutes; In the process of synthesis of ethyl amide linked armor, ethyl amide chlorine add 20 minutes can effectively prevent the critical boiling; In the process of synthesis of Nepafenac，defecate tert-butyl diazoacetate dropping time has the most prolific rate for 30min.
Keywords: Nepafenac; Non-steroidal anti-inflammatory drug; Methylthio acetamide

目  录
中文摘要 I
英文摘要 II
目录 III
1. 绪论 1
 1.1  非甾体抗炎药的现状 1
 1.2  眼科常见的NSAIDS 1     
 1.3  眼科应用NSAIDS的不良反应 4
 1.4  NSAIDS滴眼液导致角膜融解的可能机制 4
 1.5  研究开发新型的眼用NSAIDS 5
2. 奈帕芬胺的化学合成 9
 2.1  Gassman反应介绍 10
 2.2  实验室奈帕芬胺的合成 10
3. 实验部分 11
 3.1  实验仪器和试剂 11
 3.2  实验步骤 12
4. 实验结果与讨论 14
 4.1  次氯酸叔丁酯的合成 14
 4.2  甲硫基乙酰胺的合成 14
 4.3  基于苯硫基乙酰胺合成奈帕芬胺 15
5. 总结与展望 17
致谢 18
参考文献 19