7-（4-烷氧基亚氨基-3-甲基-3-甲基氨基哌啶-1-基）喹诺酮类化合物的合成及其体外抗菌活性

Synthesis and in vitro antibacterial activity of 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones.

作者信息

Wan Zhi-long, Chai Yun, Liu Ming-liang, Guo Hui-yuan, Sun Lan-ying

机构信息

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

出版信息

Yao Xue Xue Bao. 2010 Jul;45(7):860-8.

PMID:20931783

Abstract

To explore new agents of quinolone derivatives with high antibacterial activity, 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones were designed and synthesized, and their activity against gram-positive and gram-negative strains was tested in vitro. Sixteen target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis. Compounds 14k and 14m-14o show good antibacterial activity against the tested five gram-positive strains and five gram-negative strains (MIC: 0.25-16 micromg x mL(-1)), of which the most active compound 14o is 8-fold more potent than levofloxacin against S. pneumoniae (MIC: 4 microg x mL(-1)), and comparable to levofloxacin against S. aureus, S. epidermidis, E. faecalis and E. coli (MIC: 0.25-1 microg x mL(-1)), but generally less potent than gemifloxacin.

摘要

为探索具有高抗菌活性的喹诺酮衍生物新药物，设计并合成了7-(4-烷氧基亚氨基-3-甲基-3-甲基氨基哌啶-1-基)喹诺酮，并对其抗革兰氏阳性菌和革兰氏阴性菌的活性进行了体外测试。获得了16个目标化合物。通过1H NMR、HRMS和X射线晶体学分析确定了它们的结构。化合物14k和14m - 14o对所测试的5种革兰氏阳性菌和5种革兰氏阴性菌显示出良好的抗菌活性（MIC：0.25 - 16微克×毫升(-1)），其中活性最强的化合物14o对肺炎链球菌的活性比左氧氟沙星高8倍（MIC：4微克×毫升(-1)），对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和大肠杆菌的活性与左氧氟沙星相当（MIC：0.25 - 1微克×毫升(-1)），但总体活性比吉米沙星低。