（毕业学术论文设计）-喹啉酮类药物中间体的合成与应用.docVIP

lw 喹啉酮类药物中间体的合成与应用 制药工程专业***级 *** 摘要:喹啉酮类衍生物具有多种生物活性,存在于具有不同药理作用的药物分子结构中,如异喹啉酮，2-喹啉酮，4-喹啉酮等。异喹啉酮及其衍生物具有舒张血管、抗肿瘤等多种生物活性；2-喹啉酮结构是心血管药物和抗胃肠溃疡药物的重要中间体；4-喹啉酮及其衍生物具有多种优良的生物活性及低毒、安全等特性，因此对4-喹啉酮类化合物进行结构修饰，从而研究开发高选择性抗HIV整合酶抑制剂，是抗HIV药物研究的重要方向之一。本文介绍了一种合成2-喹啉酮药物中间体的方法。 本方法以二苯胺、乙酰乙酸乙酯为原料，甲苯为溶剂，三乙胺为催化剂，控制反应温度在130 ℃-140 ℃，维持反应系统沸腾状态，反应时间10小时左右，通过亲核取代反应，首先合成乙酰乙酰二苯胺。再以苯为溶剂，在浓硫酸的作用下脱水生成1-苯基-4-甲基-2-喹啉酮，控制反应温度在100 ℃左右，反应时间8小时。采用IR对目标化合物的结构进行了初步表征。 关键词：乙酰乙酰二苯胺；1-苯基-4-甲基-2-喹啉酮；亲核取代反应； 二苯胺；乙酰乙酸乙酯；异喹啉酮；4-喹啉酮 The Synthesis and Application of Quinolinone Drug Intermediates Dengliqun,Grade 2008,Pharmarcettical Engineering Abstract: Quinolinone derivatives with multiple biological activities, exist with different pharmacological action of the drug in the molecular structure,such as isoquinolinone,2-quinolinone,4-quinolinone.Isoquinolone derivatives can dilate blood vessels,antitumor and other biological acivity;2-quinolinone structure is cardiovascula -r drugs and resistance to gastrointestinal ulcer drugs are important intermediates;4- quinolinone derivatives have a variety of good biological activity and low toxicity, safety and other features, so the 4-quinoline ketone compound modification, thereby research and development of high selectivity of HIV integrase inhibitor, anti HIV drug research is one of the important directions .This paper introduces a synthesis of 2-quinoline ketone intermediates. 4-methyl-1-phenyl-2-quinolinone were synthesized from diphenylamine also and s -ome ethyl acetoacetate via nucleophilic substitution reaction and dehydration.In the first step using toluene as solvent and using triethylamine as catalyst then produce acetoacetdiphenylamine .In the second step the solvent is benzene and the catalyst is concentrated sulfuric acid. Using IR to learn the rude structure of target compound. Key words:acetoacetdiphenylamine; 1-phenyl-4-methyl-2-quinolinone; nucleophilic substitution reaction ; diphenylamine; ethyl acetoacetate; isoquinolinone;4- quinolinone 1 前言 1.1