کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1394616 1501174 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis, activity and pharmacokinetics of novel antibacterial 15-membered ring macrolones
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis, activity and pharmacokinetics of novel antibacterial 15-membered ring macrolones
چکیده انگلیسی

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.

Figure optionsDownload as PowerPoint slideHighlights
► New macrolone derivatives with oxygen(s) in the linker have been synthesized.
► Excellent antibacterial activity especially against Haemophilus influenzae has been obtained.
► Particular transformations generated compounds with improved oral bioavailability.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 46, Issue 8, August 2011, Pages 3388–3397
نویسندگان
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