Synthesis, activity and pharmacokinetics of novel antibacterial 15-membered ring macrolones
Synthesis, activity and pharmacokinetics of novel antibacterial 15-membered ring macrolones
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DOI：
10.1016/j.ejmech.2011.05.002
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发表时间：
2011-08-01
影响因子：
6.7
通讯作者：
Spaventi, Radan
中科院分区：
文献类型：
--
作者：
Fajdetic, Andrea;Vinter, Adrijana;Spaventi, Radan
报道了由阿奇霉素衍生的一类新型大环内酯类抗生素--大克隆类抗生素的合成、抗菌活性和药代动力学性质。筛选出的化合物对主要的红霉素耐药呼吸道病原菌表现出良好的抗菌活性。然而，大多数化合物缺乏良好的生物利用度。异丙酯、化合物35和带有细长连接子29的大克隆衍生物在大鼠中显示出最好的口服生物利用度，两者都具有良好的整体微生物学特征，解决了链球菌的诱导和构成MLSb以及外排介导的大环内酯类耐药性，而化合物29对葡萄球菌的抗药性更强。(C)2011年爱思唯尔·马森公司。版权所有。
Synthesis, antibacterial activity and pharmacokinetic properties of a novel class of macrolide antibiotics-macrolones-derived from azithromycin, comprising oxygen atom(s) in the linker and either free or esterified quinolone 3-carboxylic group, are reported. Selected compounds showed excellent antibacterial potency towards key erythromycin resistant respiratory pathogens. However, the majority of compounds lacked good bioavailability. The isopropyl ester, compound 35, and a macrolone derivative with an elongated linker 29 showed the best oral bioavailability in rats, both accompanied with an excellent overall microbiology profile addressing inducible and constitutive MLSb as well as efflux mediated macrolide resistance in streptococci, while compound 29 is more potent against staphylococci. (C) 2011 Elsevier Masson SAS. All rights reserved.