2,3-二氢喹啉-4(1H)-酮缩氨基脲类化合物的设计、合成及抗真菌活性研究  

Design,synthesis and evaluation of antifungal activity of 2,3dihydroquinoline-4(1H)-one semicarbazone derivatives

作　　者：梁振[1] 孙寰宇[1] 李传玲[1] 韩晓丹[1] 宋培鲁[1] 苏昕[1] 郭春[1] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《中国药物化学杂志》2013年第2期99-105,共7页Chinese Journal of Medicinal Chemistry

基　　金：国家十一五"重大新药创制"科技重大专项(2009ZX09301-012)

摘　　要：目的合成一系列二氯-2,3-二氢喹啉-4(1H)-酮缩氨基脲类化合物并测定其体外抗真菌活性。方法以二氯苯胺和丙烯酸为起始原料,经加成、环合制得中间体5,7-二氯-2,3-二氢喹啉-4(1H)-酮和6,8-二氯-2,3-二氢喹啉-4(1H)-酮;中间体与各种N4-取代的氨基脲缩合得到目标化合物;采用二倍浓度稀释法测试各目标化合物的体外抗真菌活性,实验选用9种临床上常见的致病真菌为测试菌株,以氟康唑为阳性对照药。结果与结论合成的24个化合物均未见文献报道,其结构经1H-NMR、MS谱确证;活性测试结果表明,多个目标化合物对测试真菌表现出较好的体外抑菌活性。In recent years, the incidence of fungal infections has reached alarming proportions, and the latest market outlook from data monitor shows that the rate of invasive fungal infection is increasingly rising specially. So it is of great significance to develop more effective and safe antifungal agents with novel mechanism of action. The target compounds were designed based on the bioisosterism and combination principle in drug design, by substituting the sulphur atom of thiochromanones with nitrogen giving the 2,3-dihydroquinolin-4（1H）-one scaffold and combine this moiety with semicarbazones which is the pharmacophore of cysteine protease inhibitors to give the scaffold of 2,3-dihydroquinolin-4（1H）-one semicarbazone. Totally twen- ty-four 2,3-dihydroquinoline-4 （1H）-one semicarbazone derivatives were synthesized and their structures were confirmed by MS and 1H-NMR. The antifungal assay was carded out in vitro by two-fold dilution method, with fluoconazole as the control drug. The result showed that all the compounds displayed antifungal activities against the tested fungi, T. rubrum, C. albicans, M. gypseum, A. fumigatus, C. neoformans, R. rubra, T. verrucosum ,Rhizopus and Aspergillus, in different levels, some of which showed better activities. The preliminary structure activity relationships were summarized.

关 键 词：5 7-二氯-2 3-二氢喹啉-4(1H)-酮缩氨基脲 6 8-二氯-2 3-二氢喹啉-4(1H)-酮缩氨基脲 合成 抗真菌活性 

分 类 号：R914[医药卫生—药物化学]