title: Synthesis and antibacterial activity of isomeric 15-membered azalides.
abstract: A series of 3-keto and 3-O-acyl derivatives of both 6-O-alkyl-8a-aza-8a-homoerythromycin A and 6-O-alkyl-9a-aza-9a-homo-erythromycin A were synthesised and tested against Gram-positive and Gram-negative bacteria. Derivatives of 8a-aza-8a-homoerythromycin A have potent antibacterial activity against not only azithromycin-susceptible strains, but also efflux (M) and inducible macrolide-lincosamide-streptogramin (iMLSB) resistant Gram-positive pathogens, while the corresponding 9a-isomers were less active. Introduction of an additional ring such as 11,12-cyclic carbonate reduced antibacterial activity of both series. 3-Keto and 3-O-(4-nitrophenyl)-acetyl derivatives of 6-O-methyl-8a-aza-8a-homo-erythromycin A show typical macrolide pharmacokinetics in preliminary in vivo studies in mice, and their in vivo efficacy is demonstrated.
authors.affiliation: GSK Research Centre Zagreb Ltd., Prilaz baruna Filipovica 29, 10000 Zagreb, Croatia.
authors.forename: Sulejman
authors.initials: S
authors.lastname: Alihodzic
authors.forename: Andrea
authors.initials: A
authors.lastname: Fajdetic
authors.forename: Gabrijela
authors.initials: G
authors.lastname: Kobrehel
authors.forename: Gorjana
authors.initials: G
authors.lastname: Lazarevski
authors.forename: Stjepan
authors.initials: S
authors.lastname: Mutak
authors.forename: Drazen
authors.initials: D
authors.lastname: Pavlovic
authors.forename: Vlado
authors.initials: V
authors.lastname: Stimac
authors.forename: Hana
authors.initials: H
authors.lastname: Cipcic
authors.forename: Miroslava Dominis
authors.initials: MD
authors.lastname: Kramaric
authors.forename: Vesna
authors.initials: V
authors.lastname: Erakovic
authors.forename: Andreja
authors.initials: A
authors.lastname: Hasenöhrl
authors.forename: Natasa
authors.initials: N
authors.lastname: Marsic
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schoenfeld
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides