Synthesis and antibacterial evaluation of novel 4″-glycyl linked quinolyl-azithromycins with potent activity against macrolide-resistant pathogens
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- 作者：Dražen Pavlović ; dpavlovic@hotmail.fr" class="auth_mail" title="E-mail the corresponding author ; Stjepan Mutak
- 关键词：MLSB ; macrolide&ndash ; lincosamide&ndash ; streptogramin B antibiotics ; HBTU ; O-(benzotriazol-1-yl)-N ; N ; N&prime ; N&prime ; -tetramethyluronium hexafluorophosphate ; DIPEA ; diisopropylethylamine ; SAR ; structure&ndash ; activity relationships
- 刊名：Bioorganic & Medicinal Chemistry
- 出版年：2016
- 出版时间：15 March 2016
- 年：2016
- 卷：24
- 期：6
- 页码：1255-1267
- 全文大小：869 K
文摘
A new azithromycin-based series of antibacterial macrolones is reported, which features the use of a 4″-ester linked glycin for tethering the quinolone side chain to the macrolide scaffold. Among the analogs prepared, compounds 9e and 22f with a quinolon-6-yl moiety were found to have potent and well-balanced activity against clinically important respiratory tract pathogens, including erythromycin-susceptible and MLSB resistant strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae. In addition, potential lead compounds 9e and 22f demonstrated outstanding levels of activity against Moraxella catarrhalis and inducibly MLSB resistant Staphylococcus aureus. The best member of this series 22f rivals or exceeds, in potency, some of the most active ketolide antibacterial agents known today, such as telithromycin and cethromycin.