title: Repromicin derivatives with potent antibacterial activity against Pasteurella multocida.
abstract: Reductive amination of repromicin with polyfunctional amines has led to new macrolide antibacterial agents, some of which are highly potent against the Gram-negative pathogen Pasteurella multocida both in vitro and in a mouse infection model. A key element in this discovery was the recognition that among certain known macrolides increasing lipophilicity results in diminished in vivo activity. One repromicin derivative, 20-[N-[3-(dimethylamino)-propyl]-N-L-alanylamino]-20-deoxorepro micin (35), was selected for advanced evaluation. At 5 mg/kg, a single subcutaneous dose was found to control induced pasteurellosis in swine and induced respiratory disease in cattle.
authors.affiliation: Central Research Division, Pfizer Inc., Groton, Connecticut 06340, USA. mcfarland@pfizer.com
authors.forename: J W
authors.initials: JW
authors.lastname: McFarland
authors.forename: S J
authors.initials: SJ
authors.lastname: Hecker
authors.forename: B H
authors.initials: BH
authors.lastname: Jaynes
authors.forename: M R
authors.initials: MR
authors.lastname: Jefson
authors.forename: K M
authors.initials: KM
authors.lastname: Lundy
authors.forename: C B
authors.initials: CB
authors.lastname: Vu
authors.forename: E A
authors.initials: EA
authors.lastname: Glazer
authors.forename: S A
authors.initials: SA
authors.lastname: Froshauer
authors.forename: S F
authors.initials: SF
authors.lastname: Hayashi
authors.forename: B J
authors.initials: BJ
authors.lastname: Kamicker
authors.forename: C P
authors.initials: CP
authors.lastname: Reese
authors.forename: J A
authors.initials: JA
authors.lastname: Olson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D007933:Leucomycins / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018942:Macrolides; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010326:Pasteurella Infections / Q000188:drug therapy / Q000662:veterinary; D016979:Pasteurella multocida / Q000187:drug effects*; D015645:Tylosin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C105327:20-(N-(3-(dimethylamino)propyl)-N-alanylamino)-20-deoxorepromicin; D000900:Anti-Bacterial Agents; D007933:Leucomycins; D018942:Macrolides; C052318:tylosin B; C060286:rosaramicin; D015645:Tylosin