基于甲硫基乙酰胺的奈帕芬胺合成

化工論文編號:HG114  論文字數(shù):9797,頁數(shù):25

 目  錄
中文摘要 I
英文摘要 II
目錄 III
1. 緒論 1
 1.1  非甾體抗炎藥的現(xiàn)狀 1
 1.2  眼科常見的NSAIDS 1     
 1.3  眼科應(yīng)用NSAIDS的不良反應(yīng) 4
 1.4  NSAIDS滴眼液導(dǎo)致角膜融解的可能機制 4
 1.5  研究開發(fā)新型的眼用NSAIDS 5
2. 奈帕芬胺的化學(xué)合成 9
 2.1  Gassman反應(yīng)介紹 10
 2.2  實驗室奈帕芬胺的合成 10
3. 實驗部分 11
 3.1  實驗儀器和試劑 11
 3.2  實驗步驟 12
4. 實驗結(jié)果與討論 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. 總結(jié)與展望 17
致謝 18
參考文獻 19

摘  要：非甾體抗炎藥（NSAIDS）具有抗炎、抗過敏和止痛作用，且無皮質(zhì)類固醇的不良反應(yīng)，因此，其在眼科的應(yīng)用日益受到重視。但是常用的幾種非甾體抗炎藥在使用過程中伴隨著一定的副作用。為了減少不良反應(yīng)的發(fā)生，尋求安全、有效的抗炎藥物，近年來國內(nèi)外學(xué)者對非甾體抗炎藥的眼部應(yīng)用進行了深入的研究，認為對其進行結(jié)構(gòu)改造或制成前體藥物是減少不良反應(yīng)的有效途徑。
 奈帕芬胺是新一代的非甾體類抗炎藥，主要用于治療白內(nèi)障手術(shù)相關(guān)性疼痛和炎癥。經(jīng)眼部給藥后，可迅速穿過角膜，并在眼組織水解酶的作用下轉(zhuǎn)化為氨芬酸，它能迅速到達靶位點發(fā)揮作用。本次論文的主要工作是基于甲硫基乙酰胺來合成奈帕芬胺，并在此基礎(chǔ)上做工藝放大試驗，研究其工藝放大過程中遇到的問題難點。經(jīng)過多次的實驗研究，我們發(fā)現(xiàn)：在次氯酸叔丁酯合成過程中，避光環(huán)境下，用液氮控溫至零度，反應(yīng)時間為5min時有最高產(chǎn)率；甲硫基乙酰胺的合成過程中，氯乙酰胺的滴加時間為20min時可以有效防止暴沸；奈帕芬胺的合成過程中，次氯酸叔丁酯的滴加時間為30min時有最高產(chǎn)率。
 關(guān)鍵詞：奈帕芬胺；非甾體抗炎藥；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