title: Synthesis and biological properties of 4''-O-acyl derivatives of 8a-Aza-8a-homoerythromycin.
abstract: A series of 4''-O-acyl derivatives of 8a-aza-8a-homoerythromycins A were synthesized and tested against Gram-positive and Gram-negative bacteria. Derivatives of 8a-aza-8a-homoerythromycin A have potent anti-bacterial activity against not only azithromycin-susceptible strains, but also efflux (M) and inducible macrolide-lincosamide-streptogramin-resistant Gram-positive pathogens. These compounds show moderate to high clearance and low oral bioavailability in preliminary in vivo pharmacokinetic studies in rat.
authors.affiliation: GSK Research Centre Zagreb Ltd, Zagreb, Croatia. vlado.z.stimac@gsk.com
authors.forename: Vlado
authors.initials: V
authors.lastname: Stimac
authors.forename: Sulejman
authors.initials: S
authors.lastname: Alihodzic
authors.forename: Gorjana
authors.initials: G
authors.lastname: Lazarevski
authors.forename: Stjepan
authors.initials: S
authors.lastname: Mutak
authors.forename: Zorica Marusic
authors.initials: ZM
authors.lastname: Istuk
authors.forename: Andrea
authors.initials: A
authors.lastname: Fajdetic
authors.forename: Ivana
authors.initials: I
authors.lastname: Palej
authors.forename: Hana Cipcic
authors.initials: HC
authors.lastname: Paljetak
authors.forename: Natasa
authors.initials: N
authors.lastname: Marsic
authors.forename: Jasna
authors.initials: J
authors.lastname: Padovan
authors.forename: Branka
authors.initials: B
authors.lastname: Tavcar
authors.forename: Vesna
authors.initials: V
authors.lastname: Erakovic Haber
mesh_terms: D000215:Acylation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002384:Catalysis; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C544242:8a-aza-8a-homoerythromycin; D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D004917:Erythromycin