摘要：药物的研究是关乎人们健康的焦点。四唑基的结构清晰、功能多样、药物性多样化，有很好的发展前景。CA-4作为微管蛋白抑制剂,对微管聚合和细胞有丝分裂具有很高的抑制活性,同时对秋水仙碱促进的微管聚合有竞争性抑制作用,是第一个正在开发的破坏肿瘤血管系统的抗癌药。科学家为了提高CA-4的活性和降低毒副作用,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。微管是细胞骨架的主要组成部分，在维持细胞形态、信号传导、细胞分裂等过程中起着重要作用。微管蛋白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。75020

毕业论文关键词： 微管蛋白抑制剂；CA4；四唑基；结构修饰

Triazolyl Modification of Tubulin Inhibitor CA4 and Its Derivatives

Abstract: Drug research is about the focus of people's health。 Triazole-based structure is clear, versatile, drug-based persification, there is a good development prospects。 CA-4, as a tubulin inhibitor, has a high inhibitory activity against microtubule polymerization and cell mitosis, and has a competitive inhibitory effect on colchicine-promoted microtubule polymerization and is the first to develop a tumor System of anticancer drugs。 In order to improve the activity of CA-4 and to reduce the toxic and side effects, the A-ring, the B-ring and the bridging linkages of the two rings were modified to obtain a series of CA-4 analogues。 Microtubules are a major component of the cytoskeleton and play an important role in maintaining cell morphology, signal transduction, and cell pision。 Tubulin has become one of the 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; CA4; triazolyl; structural modification

目录

前言2

1 抗肿瘤药物2

1。1 抗肿瘤药物发展前景2

1。2 抗肿瘤药物分类2

1。3 CA-4及其类似物的研究进展3

2 研究目的、理论意义和实际应用价值4

2。1 研究目的4

2。2 理论意义与实际应用价值4

3 文献综述5

3。2四氮唑类化合物生物活性研究进度5

4 本实验研究内容的探讨7

4。1研究目标、研究内容和拟采用合成路线7

4。1。1 研究目标7

4。1。2 研究内容7

4。1。3 拟采用合成路线7

5可行性分析8

6 实验室注意事项8

7 实验过程9

7。1 wittig反应9

7。1。1实验药品9

7。1。2实验仪器9

7。1。3 实验步骤9

7。2 氰基化反应9

  7。2。1 实验药品10

7。2。2 实验仪器10

7。2。3 实验步骤10

7。3氰基转化四氮唑反应11

7。3。1 实验药品11

7。3。2 实验仪器11