【作者】 朱小康；

【导师】 王玉良；

【作者基本信息】 四川大学 ， 有机化学， 2005， 硕士

【摘要】 杂环类化合物中有许多高效医药和农药,使用量少,成本低,环境污染小,且对人、畜和鱼鸟低毒,所以杂环类药物的研究开发一直是医药界和农药界的一大热点。研究表明“2-取代亚肼基-1, 3-二硫杂环戊烷”类衍生物具有较好的抑杀菌活性,对一些细菌、真菌和昆虫等都有抑制或灭杀能力,是一类值得研究的新化合物。为了拓展此类化合物的应用,本文致力于该类化合物的合成与抑菌活性研究并取得了一些阶段性结果。药物定量构效关系在指导目标化合物分子的设计与合成,帮助了解药物的作用机制,预测化合物的生物活性等方面有重要的作用。本文结合Free-Wilson的设计模式设计合成了以下几类具有(潜在)生物活性的化合物。1)将取代芳氧乙酸制成取代芳氧乙酰氯与活性母体2-亚肼基-1, 3-二硫杂环戊烷相结合, 合成了六个未见文献报道的2-取代芳氧乙酰亚肼基-1, 3-二硫杂环戊烷类衍生物。所有的目标化合物的结构均经过MS, IR, 1H NMR 和元素分析确证。2)将杀菌剂二苯醚与氯乙酸反应合成苯氧基苯氧乙酸,再将苯氧基苯氧乙酸制成酰氯与母体2-取代亚肼基-1, 3-二硫杂环戊烷联接,在适当的温度和适当的酸碱度中反应可以进行, 生成2-苯氧基苯氧乙酰亚肼基-1, 3-二硫杂环戊烷类衍生物。所有的目标化合物的结构均经过MS, IR, 1H NMR 和元素分析确证。3)选择五个目标化合物进行抑菌活性测试发现:它们对金黄色葡萄球菌、大肠杆菌、白色念珠菌、变形杆菌等七种菌种都有不同程度的抑制作用。通过更多还原

【Abstract】 The heterocyclic derivatives have the extensive application and the research values in the medicine and agrochemical. Some research works have showed “2-substituted hydrazono-1, 3-dithocyclopentane”derivatives have good bioactivity. It is an important precursor for us to obtain more new compounds, which have higher effect, wilder application, better selectivity and lower toxicity. This article concentrates on the synthesis and anti-bactericidal activities of the new 2-Substituted aryloxy acetyl hydrazono -1, 3-dithiocyclopentan derivatives. Quantitative Structure-Activity Relationships (QSAR) plays an important role in drug’s discovery, because it can predict compound’s bioactivity and helps us to discover the relationship of the pharmacal effect and the target molecules (TM) structure. On the basis of Free-Wilson model, two kinds of target molecules owning potential bioactivity are designed. The following innovated results were achieved: (1) Six new 2-substituted aryloxy acetyl hydrazono-1, 3-dithocyclopentane have been designed and synthesized. All of them are reported for the first time and their structures have been confirmed by IR, 1H NMR, MS and elemental analysis. (2) The other kind of 2-Substituted diphenoxyl acetyl hydrazono-1, 3-dithocyclopentane derivatives have been synthesized via arylation the biphenyl acetyl chlorine and 2-hydrazono-1,3-dithocyclopentane. Their structures have been confirmed by IR, 1H NMR, MS and elemental analysis. (3) The anti-bactericidal test was carried out. We chosen five targets and seven kinds of bacterium in this test. Studied on the test and we found the following results: a). all of the tested compounds have good anti-bacteria activity. The targets have antimicrobial activity on S. aureus, E. coli, S. Ligneres, P.Vulgaris and D.cata, et al. b). The target which contains fluoro-substitution has the best anti-bacteria activity among all this targets. (4) All the target molecules have more extensive anti-bactericidal activity than tricyclazole and thiophanate-methyl (on sale), which are anti-bacteria agents widely used. The thorough researches in future can provide probably the practical good anti-bacteria compounds. These studies give a good basis to expand the researches and applications of the 2-Substituted aryloxy acetyl hydrazono-1, 3-dithocyclopentane and the related derivatives.更多还原