摘要：药物的研究是关乎人们健康的焦点。脒盐的结构简单、功能多样，有很好的发展前景。CA-4是一种可以抑制有丝分裂的物质,它对微管的膨胀和细胞的分裂起到了关键性的作用,而且它对肿瘤细胞有着聚合的功能，是目前正在研究的关于肿瘤蔓延的抗肿瘤药。为了提高CA-4的药理活性和降低带来的不良反应，对其A环、B环及连接两个环的桥键进行修饰,得到了一系列CA-4类似物。在细胞的组织中，微管是核心的组成元素，微管有阻止信号的传导、癌细胞的增殖、基因的恶化等作用。微管抑制剂成为研究与开发全新抗癌药物的重要靶点之一。通过国内外的文献分析整理，了解到具有抗癌活性的微管蛋白聚合抑制剂 CA-4 衍生物的研究现状。CA4结构简单，作用机制新颖，以它为先导化合物研究出了许多的类似物并筛选出一些新药候选物。而且对其衍生物的研究也为此类化合物作用机制研究提供了帮助。该类化合物结构的修饰研究对制药行业也有着重要的意义。69517

毕业论文关键词： 微管蛋白抑制剂；CA4；脒盐；结构修饰

Study on amidine salt modification of tubulin inhibitor CA4 and its derivatives

Abstract：Drug research is about the focus of people's health. Amidine salt structure is simple, versatile, has a good development prospects.CA-4 is a substance that inhibits mitosis, which plays a key role in the expansion of microtubules and the pision of cells, and it has a function of aggregation of tumor cells and is currently being studied against tumor spread medicine. In order to improve the pharmacological activity and the adverse reactions of CA-4, a series of CA-4 analogues were obtained by modifying the A-ring, B-ring and the bridging linkages. In the organization of cells, microtubules are the core of the composition of elements, microtubules have to prevent the transmission of the signal, cancer cell proliferation, gene deterioration and so on. Microtubule inhibitors are one of the most important targets for the research and development of new anticancer drugs. Through the literature analysis at home and abroad, to understand the anticancer activity of tubulin polymerization inhibitor CA-4 derivatives of the research status quo. CA4 has a simple structure, a new mechanism of action, and has developed a number of analogues for the lead compounds and screened out some new drug candidates. And the study of its derivatives also contributed to the study of the mechanism of action of such compounds. The modification of the structure of these compounds is also of great significance to the pharmaceutical industry.

Key words： Tubulin inhibitor;  Combretastatin A-4； Amidine salt; Structural modification 

目录

绪论1

1 研究目的、研究价值和意义2

1.1 研究目的2

1.2 研究价值和意义2

2 文献综述3

2.1CA-4及其衍生物脒盐的研究3

2.2脒类化合物生物活性研究进度4

2.3脒盐的发展概况及存在的问题4

2.4钯催化氰化芳基甲磺酸酯5

2.5酚羟基用对甲苯磺酰基保护6

3 本实验研究内容的探讨7

3.1研究目标、研究内容和拟采用合成路线7

3.1.1 研究目标7

3.1.2 研究内容7

3.1.3 拟采用合成路线7

4 可行性分析8

5 脒盐的合成方法9

5.1 氰的胺解法9

5.2催化合成法9

5.3酰胺法10

6 实验室注意事项11

7 实验过程12

7.1 wittig反应12

7.1.1实验药品12

7.1.2实验仪器12

7.1.3 实验步骤12

7.1.4反应方程式12

7.2 氰基化反应12

7.2.1 实验药品12

7.2.2 实验仪器13

7.2.3 实验步骤13

7.2.4反应方程式13