title: Synthesis, activity and pharmacokinetics of novel antibacterial 15-membered ring macrolones.
abstract: 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.
authors: GlaxoSmithKline Research Center Zagreb Ltd., Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. andrea.fajdetic@glpg.com
authors: Andrea
authors: A
authors: Fajdetić
authors: Adrijana
authors: A
authors: Vinter
authors: Hana Čipčić
authors: HČ
authors: Paljetak
authors: Jasna
authors: J
authors: Padovan
authors: Ivana Palej
authors: IP
authors: Jakopović
authors: Samra
authors: S
authors: Kapić
authors: Sulejman
authors: S
authors: Alihodžić
authors: Darko
authors: D
authors: Filić
authors: Marina
authors: M
authors: Modrić
authors: Nada
authors: N
authors: Košutić-Hulita
authors: Roberto
authors: R
authors: Antolović
authors: Zrinka Ivezić
authors: ZI
authors: Schoenfeld
authors: Stjepan
authors: S
authors: Mutak
authors: Vesna
authors: V
authors: Eraković Haber
authors: Radan
authors: R
authors: Spaventi