引入苯并含氮杂环的嘧啶及咪唑类衍生物的合成

【作者】 彭志鸿；

【导师】 安德烈；

【作者基本信息】 湖南大学 ， 有机化学， 2002， 硕士

【摘要】 在医药和农药的研究和开发中，含氮杂环化合物发挥着重要作用，是当今药物研究的一大热点。但对苯并杂环化合物3，4-二氢-2(1氢)羰基喹喔啉、1，2，3，4-四氢喹喔啉、2，3-二氢，1，4-苯并噁嗪和2，3-二氢苯并噁唑的研究相对较少。实际上，它们在一些药物中也发挥着重要作用，可能是这些药物的活性中心，具有生物活性。 嘧啶类及咪唑类化合物广泛存在于自然界、结构简单，在药物开发和研究中占有非常突出的地位，对其研究也非常活跃。许多临床药物都含有嘧啶及咪唑。同时含有嘧啶或咪唑的新研制的众多化合物也具有生物活性。因而可以确信嘧啶或咪唑是具有生物活性的。 定量构效关系研究在预测化合物的生物活性、帮助了解药物的作用机制方面有一定的作用，能够指导目标分子设计。本文结合Free-Wilson模式的基本思想，设计了两类具有潜在生物活性的新型目标分子。 为了进行目标分子的合成研究，首先研究了苯并杂环化合物的合成。通过对它们不同的合成方法的比较，结合本研究室以前的研究，优化和完善了这四种苯并杂环化合物的合成方法，可以用价廉易得的原料简单直接地制备它们。同时利用其具有的仲胺性质，成功地制备了几个相关衍生物。 设计并合成了四个N-氯乙酰和N，N’-二氯乙酰取代的苯并含氮杂环中间体。它们分别与2-巯基-4，6-二甲基嘧啶反应被导入嘧啶结构中，与2-巯基苯并咪唑反应被导入咪唑结构中。新化合物的结构经MS高分辨NMR和元素分析得到确证。更多还原

【Abstract】 In the research and exploitation of medicine and pestcide, hetrocyclic compounds containing nitrogen play an important role. It is a focus of the research of novel Pharmaceuticals. But there are a little research on nitrogen-containing benzoheterocyclic compounds: 3,4-dihydro-2(1H) quinoxalinone, 1,2,3,4-tetrahydro-quino-xaline, 2,3-dihydro-l,4-benzo- xazine, and 2,3-dihydrobenzoxazole. In fact, they play an important role in many Pharmaceuticals, perhaps are their bioactivity’s center. Therefore they maybe have potential bioactiviry.The pyrimidines or the imidazolines, whose structures are simple, exist in nature wildly. They are vital role in the research and exploitation of Pharmaceuticals. The research on them is hot. Pyrimidine and imidazoline exist in a large number of medicines. Meantime, lots of new compounds containing pyrimidinecycle or Imidazolinecycle own potential bioactivity. So it is sure to say that They have bioactivity.The research of quantitative structure-activity relationships(QSAR), which can predict compound’s bioactivity, helps to know the pharmaceutical effect and design target molecular(TM). On the basis of free-wilson model, two kinds of target molecular owning potential bioactiviry are designed, as following:In order to research the synthesis of target molecular, the synthesis of nitrogen-containing benzoheterocyclic compounds has been synthsized firstly. Compared with different synthetic methods and based on the preceding researches in our laboratory, the synthesis method of those nitrogen-containing benzoheterocyclic compounds was optimized. It is simple and direct to prepare from inexpensive and ease materials. Several derivates were prepared successfully on their properties ofsecondary ammonia.Four types of N-chloroacetyl and N, N’-dichloroacetyl substituted nitrogen-Containing intermediate compounds were successfully designed and synthesized. Their were treated with 2-mercapto-4,6-dimethy pyrimidine respectively, they were introduced into pyrimide structure. In same method, reated with 2-mercapto-benzoic-midazoles respectively, they were introduced into imidazoline structure. The structures of all new compounds were identified by MS, high resolution-NMR and elemental analysis.更多还原