【摘要】：本文綜述了抑郁癥與抗抑郁藥物的發(fā)展歷程，并著重介紹了新型抗抑郁藥維拉佐酮。維拉佐酮于2011年獲FDA批準(zhǔn)成為成人重度抑郁癥的臨床治療藥物，因具有SSRI與5-HT1A受體激動(dòng)劑雙藥效團(tuán)，與傳統(tǒng)抗抑郁藥相比起效更快、選擇性更好、藥效更強(qiáng)。鑒于其良好的應(yīng)用前景，本文對(duì)合成維拉佐酮的關(guān)鍵中間體3-(4-氯丁基)-5-氰基吲哚的合成進(jìn)行了研究。 首先采用路線一“吲哚-吲哚啉-吲哚”合成法，以吲哚、亞硫酸氫鈉為原料，經(jīng)過加成、N-�；Ｗo(hù)、溴化和脫�；Ｗo(hù)得到了5-溴吲哚，，但在繼續(xù)以氰化亞銅為氰化試劑反應(yīng)時(shí)未能成功制備5-氰基吲哚。采用路線二L-B吲哚合成法，以間甲基苯胺為原料經(jīng)N-�；Ｗo(hù)、硝化、重氮化、Sandmeyer氰基化和還原環(huán)化最終合成了5-氰基吲哚。最后以5-氰基吲哚為原料、4-氯丁酰氯為酰基化試劑經(jīng)Friedel-Crafts�；磻�(yīng)合成了3-(4-氯丁�；�)-5-氰基吲哚。 本文分別對(duì)采用的路線一、路線二的各步反應(yīng)的影響因素及相關(guān)機(jī)理進(jìn)行了探討，對(duì)已得到的產(chǎn)物及中間體結(jié)構(gòu)經(jīng)IR、1HNMR等進(jìn)行了表征。
[Abstract]:In this paper, the development of depression and antidepressants was reviewed, and the new antidepressant verazodone was introduced. Verazodone was approved by FDA in 2011 as a clinical drug for severe depression in adults. Because of its dual drug efficacy of SSRI and 5-HT1A receptor agonists, verazodone is more effective, more selective and more effective than traditional antidepressants. In view of its good application prospect, the synthesis of 3-(4-chlorobutyl)-5-cyanoindole, a key intermediate for the synthesis of verrazolone, was studied in this paper. Firstly, 5-bromoindole was synthesized from indole and sodium bisulfite by route 1 "indole-indoline-indole" synthesis method. 5-bromoindole was obtained by addition, N-acyl protection, bromination and deacylation protection, but 5-cyanoindole could not be successfully prepared when cuprous cyanide was used as cyanide reagent. 5-cyanoindole was synthesized by route diL-B indole synthesis with m-methylaniline as raw material under N-acyl protection, nitrification, diazotization, Sandmeyer cyclization and reductive cyclization. Finally, 3-(4-chlorobutyryl)-5-cyanoindole was synthesized by Friedel-Crafts acylation with 5-cyanoindole as raw material and 4-chlorobutyryl chloride as acylation reagent. In this paper, the influencing factors and related mechanisms of each step of route 1 and route 2 were discussed, and the structures of the obtained products and intermediates were characterized by IR,1HNMR and so on.
【學(xué)位授予單位】：天津理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.5

【共引文獻(xiàn)】

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