title: 4''-O-(omega-Quinolylamino-alkylamino)propionyl derivatives of selected macrolides with the activity against the key erythromycin resistant respiratory pathogens.
abstract: Four macrolides-6-O-methyl-8a-aza-8a-homoerythromycin, clarithromycin, azithromycin and azithromycin 11,12-cyclic carbonate, have been selected for the construction of a series of new quinolone derivatives. The quinolone moiety is connected to the macrolide scaffold via a diaminoaklyl 4''-O-propionyl ester chain of varying length. At the terminus the linker is attached via one of the nitrogen atoms in the linker at C(6) or C(7) of the quinolone. Many of compounds described, particularly clarithromycin derivative 37, and azithromycin derivatives 48 and 55, exhibited excellent antibacterial activity against a wide range of clinically relevant macrolide-resistant organisms, with profiles superior to that of telithromycin, an enhanced spectrum ketolide.
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. andrea.z.fajdetic@gsk.com
authors.forename: A
authors.initials: A
authors.lastname: Fajdetić
authors.forename: H
authors.initials: H
authors.lastname: Cipcić Paljetak
authors.forename: G
authors.initials: G
authors.lastname: Lazarevski
authors.forename: A
authors.initials: A
authors.lastname: Hutinec
authors.forename: S
authors.initials: S
authors.lastname: Alihodzić
authors.forename: M
authors.initials: M
authors.lastname: Derek
authors.forename: V
authors.initials: V
authors.lastname: Stimac
authors.forename: D
authors.initials: D
authors.lastname: Andreotti
authors.forename: V
authors.initials: V
authors.lastname: Sunjić
authors.forename: J M
authors.initials: JM
authors.lastname: Berge
authors.forename: S
authors.initials: S
authors.lastname: Mutak
authors.forename: M
authors.initials: M
authors.lastname: Dumić
authors.forename: S
authors.initials: S
authors.lastname: Lociuro
authors.forename: D J
authors.initials: DJ
authors.lastname: Holmes
authors.forename: N
authors.initials: N
authors.lastname: Marsić
authors.forename: V
authors.initials: V
authors.lastname: Eraković Haber
authors.forename: R
authors.initials: R
authors.lastname: Spaventi
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011422:Propionates / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D011422:Propionates; D004917:Erythromycin