Design, synthesis and antibacterial activity of novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain
作者:Qiu-Ling Song、Bao-Qin Guo、Wen Zhang、Ping Lan、Ping-Hua Sun、Wei-Min Chen
DOI:10.1038/ja.2011.50
日期:2011.8
A set of 17 novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain were synthesized and evaluated for their antibacterial activities, which the aryltetrazolyl group was selected to replace the hetero-aryl moiety of the side chain in telithromycin for designing new compounds. The synthesis of aryltetrazolyl alkylamines was reported in detail. The antibacterial activities of new ketolides were evaluated against a number of pathogens including macrolide-resistant organisms by using telithromycin as the reference. Many of the evaluated compounds exhibited remarkable activities against both erythromycin-susceptible and erythromycin-resistant organisms such as Staphylococcus aureus (except S. aureus AD-08), Pseudomonas aeruginosa and Escherichia coli. Among these, the compound 11e exhibited excellent antibacterial potency against all the strains in comparison with others.
合成了一组17种新型酮类抗生素,具有取代芳基四氮唑的烷基侧链,并评估了它们的抗菌活性。芳基四氮唑基团的选择是为了替代泰利霉素侧链中的杂芳基,旨在设计新的化合物。详细报告了芳基四氮唑烷基胺的合成过程。新型酮类抗生素的抗菌活性是针对包括大环内酯耐药菌在内的多种病原体进行评估,使用泰利霉素作为参考。许多评估的化合物对包括金黄色葡萄球菌(除了 S. aureus AD-08)、绿脓杆菌和大肠杆菌在内的红霉素敏感菌和红霉素耐药菌表现出显著的抗菌活性。在这些化合物中,化合物11e与其他化合物相比,显示出对所有菌株的极佳抗菌效能。