标题：Synthesis and antibacterial evaluation of novel 11,4″-disubstituted azithromycin analogs with greatly improved activity against erythromycin- resistant bacteria
作者：Li X.; Ma S.; Yan M.; Wang Y.; Ma S.
作者机构：[Li, X] Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan 250012, China;[ Ma, S] 更多
通讯作者地址：[Ma, S] Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan 250012, China;
来源：European Journal of Medicinal Chemistry
关键词：11,4″-disubstituted azithromycin analogs; Antibacterial activity; Erythromycin-resistant bacteria; Synthesis
摘要：A series of novel 11,4″-disubstituted azithromycin analogs were synthesized and evaluated for their antibacterial activity. All the 11,4″-disubstituted analogs exhibited excellent activity (0.03-0.12 μg/ml) against erythromycin-susceptible Streptococcus pneumoniae, and significantly improved activity against three phenotypes of erythromycin- resistant S. pneumoniae compared with erythromycin A, clarithromycin or azithromycin. Among them, compounds 26-28 showed the most potent activity (0.25, 0.03 and 2 μg/ml) against S. pneumoniae expressing the erm gene, the mef gene and the erm and mef genes, respectively. In addition, compound 28 was the most effective (0.03 and 0.12 μg/ml) against erythromycin-susceptible S. pneumoniae and Staphylococcus aureus as well. It is noteworthy that the most active compounds described above possess the same terminal 3,5-dinitrophenyl groups on their C-4″ bisamide side chains.© 2012 Elsevier Masson SAS. All rights reserved.