新型N-苯基哌嗪喹啉类衍生物的设计与合成
发布时间：2018-09-09 18:39
【摘要】：杂环类化合物是一类非常重要的化合物，它在有机药物合成中有着十分重要实用地位，这主要取决于它们的二环和三环的衍生物在医药和农药方面具有可应用的生理活性。在这其中，1,5-苯并硫氮杂及其衍生物是一类比较重要的七元杂环化合物，它同时含有N元素和S元素。1,5-苯并硫氮杂及其衍生物之所以应用广泛，主要是因为他们具有广阔的生物活性，例如它们具有抗高血压、抗惊厥、抗癌、抗HIV、抗溃疡、抗菌等作用，另外，它们也可以作为钙离子拮抗剂，是许多止痛剂等重要药物的主要成分。例如，在人类目前广泛使用的一类临床药物—盐酸地尔硫中，就含有杂环结构。目前，1,5-苯并硫氮杂及其衍生物的合成及研究已经成为了许多药物化学家们的重要研究热点。 在医药工业中，许多喹啉化合物都是重要的药物中间体。近年来，许多含喹啉环的新型药物不断的被人们开发出来。喹啉最初是从抗疟药物—奎宁中经过蒸馏而得到的，喹啉主要应用于合成抗疟药物，如磷酸氯喹、磷酸伯胺喹和胺酚喹啉等；也可以合成重要的局部麻醉药物，如盐酸地布卡因；还可以合成解热镇痛药物辛可芬，抗菌素药物克菌定；还有抗阿米巴病药喹碘仿、氯碘喹啉、双碘喹啉等等。同时由喹啉环及其他杂环化合物还可以合成扑蛲灵和克泻痢宁。通过前人的研究，我们发现通过1,3-偶极环加成反应可以成功的构建四元、五元杂环，考虑到药物设计的拼接原理，在研究过程中，，我们把1,5-苯并硫氮杂引入到喹啉环母核中，借以期望获得有潜在生物学活性的化合物，为有机药物的筛选提供合成方法及先导化合物。 我们的主要工作是将N-苯基哌嗪作为取代基引入到喹啉杂环分子中，并通过1,3-偶极环加成反应合成了一系列结构新颖且具有潜在生物学活性的衍生物，成功的合成了一系列含N-苯基哌嗪的喹啉类衍生物。 本论文分为以下两部分： 第一部分为文献综述部分： 该部分对喹啉、1,5-苯并硫氮杂和1,2,4-VA二唑的重要合成方法以及生理、药理活性等在国内外的研究状况作了比较系统的阐述；同时还简要介绍了1,3-偶极环加成反应等对1,5-苯并硫氮杂衍生物及含喹啉基1,2,4-VA二唑啉类衍生物进行结构修饰的环合反应。 第二部分为实验部分，主要工作如下： 1、新型含苯基哌嗪取代的喹啉基1,5-苯并硫氮杂及其衍生物的合成与表征 利用新合成的1,5-苯并硫氮杂衍生物与简单对位取代的氯代肟通过1,3-偶极环加成反应得到一系列1,2,4-VA二唑并1,5-苯并二氮杂类衍生物。 2、新型含苯基哌嗪取代的喹啉基1,2,4-VA二唑啉类衍生物的合成与表征 2-（4-苯基哌嗪-1-基）-3-喹啉甲醛与对位取代的苯胺反应得到不同的亚胺，接着亚胺和简单对位取代的氯代肟通过1,3-偶极环加成反应得到一系列含喹啉基1,2,4-VA二唑啉类衍生物。 3、新型含苯基哌嗪取代的喹啉基1,3,4-VA二唑啉类衍生物的合成与表征 2-（4-苯基哌嗪-1-基）-3-喹啉甲醛与不同取代苯甲酰肼反应得到一系列新型的酰腙类化合物，然后在乙酸酐中氧化关环得到了一系列新型含喹啉基1,3,4-VA二唑啉类衍生物。 产物结构经过元素分析、MS、IR、1H NMR和13C NMR得到确认，并对其波谱性质进行了分析和讨论。
[Abstract]:Heterocyclic compounds are a very important class of compounds, which play a very important role in the synthesis of organic drugs, mainly depending on their dicyclic and tricyclic derivatives have applied physiological activities in medicine and pesticides. Cyclic compounds, which contain both N and S elements. 1,5-benzothiaza and their derivatives are widely used because they have broad biological activities, such as anti-hypertension, anticonvulsant, anticancer, anti-HIV, anti-ulcer, antibacterial and so on. In addition, they can also be used as calcium ion antagonists and are many analgesics. For example, Diltiazem hydrochloride, a widely used clinical drug, contains heterocyclic structure. At present, the synthesis and research of 1,5-benzothiazole and its derivatives have become an important research hotspot of many pharmaceutical chemists.
Quinoline compounds are important pharmaceutical intermediates in the pharmaceutical industry. In recent years, many new drugs containing quinoline rings have been developed. Quinoline was originally obtained by distillation from quinine, an antimalarial drug. Quinoline is mainly used in the synthesis of antimalarial drugs, such as chloroquine phosphate, primary aminoquine phosphate and aminophenol quinoline. It can also be used to synthesize important local anesthetics, such as dibucaine hydrochloride, antipyretic and analgesic drugs, such as cinchofen and clotridine, as well as quinolidoform, chloroiodoquinoline, bisiodoquinoline, etc. Quinoline rings and other heterocyclic compounds can also be used to synthesize chlorphenamine and clotridine. Previous studies have shown that tetrad and quintuple heterocycles can be successfully constructed by 1,3-dipolar cycloaddition reaction. Considering the splicing principle of drug design, we introduced 1,5-benzothiazide into quinoline nucleus in order to obtain compounds with potential biological activity and provide a basis for the screening of organic drugs. Synthesis methods and lead compounds.
Our main work is to introduce N-phenylpiperazine as a substituent into quinoline heterocyclic molecules and synthesize a series of novel derivatives with potential biological activities by 1,3-dipolar cycloaddition reaction. A series of quinoline derivatives containing N-phenylpiperazine were successfully synthesized.
This thesis is divided into two parts:
The first part is the literature review.
In this part, the important synthetic methods, physiological and pharmacological activities of quinoline, 1,5-benzothiazole and 1,2,4-VA diazole are systematically reviewed, and the 1,5-benzothiazole derivatives and quinoline-containing 1,2,4-VA diazoline derivatives are also briefly introduced. Structural modification of cyclization.
The second part is the experimental part. The main tasks are as follows:
1, the synthesis and characterization of novel quinoline 1,5- benzoxazide substituted phenoxy piperazine derivatives
A series of 1,2,4-VA diazo 1,5-benzodiazo derivatives were synthesized by 1,3-dipolar cycloaddition of 1,5-benzothiazole derivatives with simple para-substituted chlorooximes.
2, synthesis and characterization of a new quinoline 1,2,4-VA two azoline derivative containing phenyl piperazine.
2-(4-phenylpiperazine-1-yl) -3-quinoline formaldehyde reacts with para-substituted aniline to obtain different imines. Then imines and simple para-substituted oximes react with 1,3-dipolar cycloaddition to obtain a series of quinoline-containing 1,2,4-VA diazoline derivatives.
3, synthesis and characterization of a new quinoline 1,3,4-VA two azoline derivative containing phenyl piperazine.
A series of new acylhydrazones were synthesized by the reaction of 2-(4-phenylpiperazine-1-yl) -3-quinoline formaldehyde with different substituted benzoylhydrazines. Then a series of new quinolino-containing 1,3,4-VA diazoline derivatives were obtained by oxidative ring-closure in acetic anhydride.
The structure of the product was confirmed by elemental analysis, MS, IR, 1H NMR and 13C NMR, and its spectral properties were analyzed and discussed.
【学位授予单位】：新疆大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：O626
[Abstract]:Heterocyclic compounds are a very important class of compounds, which play a very important role in the synthesis of organic drugs, mainly depending on their dicyclic and tricyclic derivatives have applied physiological activities in medicine and pesticides. Cyclic compounds, which contain both N and S elements. 1,5-benzothiaza and their derivatives are widely used because they have broad biological activities, such as anti-hypertension, anticonvulsant, anticancer, anti-HIV, anti-ulcer, antibacterial and so on. In addition, they can also be used as calcium ion antagonists and are many analgesics. For example, Diltiazem hydrochloride, a widely used clinical drug, contains heterocyclic structure. At present, the synthesis and research of 1,5-benzothiazole and its derivatives have become an important research hotspot of many pharmaceutical chemists.
Quinoline compounds are important pharmaceutical intermediates in the pharmaceutical industry. In recent years, many new drugs containing quinoline rings have been developed. Quinoline was originally obtained by distillation from quinine, an antimalarial drug. Quinoline is mainly used in the synthesis of antimalarial drugs, such as chloroquine phosphate, primary aminoquine phosphate and aminophenol quinoline. It can also be used to synthesize important local anesthetics, such as dibucaine hydrochloride, antipyretic and analgesic drugs, such as cinchofen and clotridine, as well as quinolidoform, chloroiodoquinoline, bisiodoquinoline, etc. Quinoline rings and other heterocyclic compounds can also be used to synthesize chlorphenamine and clotridine. Previous studies have shown that tetrad and quintuple heterocycles can be successfully constructed by 1,3-dipolar cycloaddition reaction. Considering the splicing principle of drug design, we introduced 1,5-benzothiazide into quinoline nucleus in order to obtain compounds with potential biological activity and provide a basis for the screening of organic drugs. Synthesis methods and lead compounds.
Our main work is to introduce N-phenylpiperazine as a substituent into quinoline heterocyclic molecules and synthesize a series of novel derivatives with potential biological activities by 1,3-dipolar cycloaddition reaction. A series of quinoline derivatives containing N-phenylpiperazine were successfully synthesized.
This thesis is divided into two parts:
The first part is the literature review.
In this part, the important synthetic methods, physiological and pharmacological activities of quinoline, 1,5-benzothiazole and 1,2,4-VA diazole are systematically reviewed, and the 1,5-benzothiazole derivatives and quinoline-containing 1,2,4-VA diazoline derivatives are also briefly introduced. Structural modification of cyclization.
The second part is the experimental part. The main tasks are as follows:
1, the synthesis and characterization of novel quinoline 1,5- benzoxazide substituted phenoxy piperazine derivatives
A series of 1,2,4-VA diazo 1,5-benzodiazo derivatives were synthesized by 1,3-dipolar cycloaddition of 1,5-benzothiazole derivatives with simple para-substituted chlorooximes.
2, synthesis and characterization of a new quinoline 1,2,4-VA two azoline derivative containing phenyl piperazine.
2-(4-phenylpiperazine-1-yl) -3-quinoline formaldehyde reacts with para-substituted aniline to obtain different imines. Then imines and simple para-substituted oximes react with 1,3-dipolar cycloaddition to obtain a series of quinoline-containing 1,2,4-VA diazoline derivatives.
3, synthesis and characterization of a new quinoline 1,3,4-VA two azoline derivative containing phenyl piperazine.
A series of new acylhydrazones were synthesized by the reaction of 2-(4-phenylpiperazine-1-yl) -3-quinoline formaldehyde with different substituted benzoylhydrazines. Then a series of new quinolino-containing 1,3,4-VA diazoline derivatives were obtained by oxidative ring-closure in acetic anhydride.
The structure of the product was confirmed by elemental analysis, MS, IR, 1H NMR and 13C NMR, and its spectral properties were analyzed and discussed.
【学位授予单位】：新疆大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：O626
【参考文献】
相关期刊论文 前10条
1 李小六;张宏波;朱振刚;陈华;段科芳;张平竹;;微波促进1,3-偶极环加成反应合成氮杂糖苷衍生物[J];高等学校化学学报;2010年09期
2 付晓钟,袁牧,张珏,张振,刘香,张敏;1-(4-甲氧苯基)哌嗪盐酸盐的合成[J];贵阳医学院学报;1999年04期
3 Divyesh C.Mungra;Harshad G.Kathrotiya;Niraj K.Ladani;Manish P.Patel;Ranjan G.Patel;;Molecular iodine catalyzed synthesis of tetrazolo[1,5-a]-quinoline based imidazoles as a new class of antimicrobial and antituberculosis agents[J];Chinese Chemical Letters;2012年12期
4 梁诚;;喹啉及其衍生物开发与应用[J];化工文摘;2004年02期
5 潘建林,陶兰,幸勇,姚碧峰;N-苯基哌嗪的合成[J];中国现代应用药学;2001年05期
6 陈庆华;;1,3-偶极环加成反应在有机合成方面的新进展[J];有机化学;1988年03期
7 张自义;陈立民;冯小明;曾福礼;;酰氨基硫脲及其相关杂环衍生物的研究——Ⅻ.1-(α-苯基氰乙酰胺基)-3-芳酰基硫脲及3-(α-苯基氰甲基)-4-芳酰基-1,2,4-三唑-5-硫酚衍生物的合成[J];有机化学;1989年02期
8 陈庆华;谢孟\
本文编号：2233237
本文链接：https://www.wllwen.com/yixuelunwen/mazuiyixuelunwen/2233237.html
最近更新
教材专著
