喹唑啉酮类化合物的合成及抗菌作用研究

发布时间：2018-06-12 02:48

本文选题：喹唑琳酮 + 查尔酮　；参考：《延边大学》2014年硕士论文

【摘要】：目的：由于人们对抗菌药的使用不当,使得耐药菌层出不穷,作为药物研究对象,寻找到对临床耐药菌有效的化合物意义重大。方法：首先采用结构拼合原理设计,合成了化合物1-29,然后模仿含有烯酮结构转变成嘧啶硫酮的思想设计合成了化合物3a-t和化合物4a-t。采用常规合成方法合成了所有化合物,并采用氢谱,碳谱进行了结构确证。采用临床药敏筛选方法筛选出9种耐药菌,采用TCC比色法将所有化合物进行了抗多药耐药菌的活性筛选。结果：最终合成了化合物69个,经过药理活性测定,化合物1-29展示出良好的抗多药耐药菌活性,很多化合物最低抑菌浓度在0.5μg/ml,其中化合物3,6和21对革兰氏阳性和革兰氏阴性菌同样有效,化合物14可以同时对抗四种菌,我们所采用的菌株都是在临床患者身上取得并经过培养和鉴定的,因此我们筛选出的这些化合物表现出良好的抗菌活性体现出这些化合物的药用价值。很多化合物的抗菌效果优于临床现行用药氨曲南和头孢他汀。然而,嘧啶-2-硫酮类化合物活性较差,两个系列40个化合物中,没有一个化合物的最低抑菌浓度在0.5ug/ml以下。推测主要原因是化合物的溶解性较差所致。结论：经过2步,3步反应获得69个化合物,这些化合物全部经过氢谱和碳谱结构确证,抗菌活性筛选证实多个化合物抗菌活性良好,尤其是化合物14值得进一步研究与开发。
[Abstract]:Objective: due to the improper use of antimicrobial agents, drug-resistant bacteria emerge in endlessly. It is of great significance to find effective compounds for clinical drug-resistant bacteria as the object of drug research. Methods: firstly, the principle of structural assembly was used to design the drug resistant bacteria. Compounds 1-29 were synthesized, and then the compounds 3a-t and 4a-t were synthesized by imitating the idea of transforming the structure of ketene to pyrimidine thione. All the compounds were synthesized by conventional synthesis method, and their structures were confirmed by hydrogen and carbon spectra. Nine strains of drug-resistant bacteria were screened by clinical drug sensitivity screening, and all compounds were screened by TCC colorimetry. Results: finally, 69 compounds were synthesized and determined by pharmacological activity. Compounds 1-29 showed good antimicrobial activity. The minimum inhibitory concentration of many compounds was 0.5 渭 g / ml. Compounds 3 and 21 were equally effective against Gram-positive and Gram-negative bacteria, and compound 14 could be used against four strains at the same time. The strains we used were obtained from clinical patients and were cultured and identified, so the compounds we screened showed good antibacterial activity and showed the medicinal value of these compounds. The antimicrobial efficacy of many compounds is superior to that of aztreonam and cefstatatin. However, the activity of pyrimidine-2-thione compounds was poor, and none of the 40 compounds in the two series had a minimum inhibitory concentration below 0.5ug/ml. Conclusion: 69 compounds were obtained by two steps and three steps reaction, all of them were confirmed by hydrogen spectrum and carbon spectrum structure, and the antimicrobial activity screening proved that many compounds had good antibacterial activity. In particular, compound 14 is worthy of further study and development.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914

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