title: Synthesis and activity of a novel class of tribasic macrocyclic antibiotics: the triamilides.
abstract: The stereoselective synthesis of two novel series of tribasic macrocyclic antibiotics with potent in vitro activity against Pasteurella multocida and Escherichia coli strains of bacteria is described. The in vitro activity can be significantly influenced by the nature of the substituents on the C-4" aminoalcohol, with the stereochemistry of the C-4" alcohol playing a less critical role. The effect of substitution and stereochemistry on the in vivo activity in a murine model of respiratory infection is also described.
authors.affiliation: Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. michael_a_letavic@groton.pfizer.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Letavic
authors.forename: Brian S
authors.initials: BS
authors.lastname: Bronk
authors.forename: Camilla D
authors.initials: CD
authors.lastname: Bertsche
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Casavant
authors.forename: Hengmiao
authors.initials: H
authors.lastname: Cheng
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Daniel
authors.forename: David M
authors.initials: DM
authors.lastname: George
authors.forename: Shigeru F
authors.initials: SF
authors.lastname: Hayashi
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Kamicker
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Kolosko
authors.forename: Laura J L
authors.initials: LJ
authors.lastname: Norcia
authors.forename: Vanessa D
authors.initials: VD
authors.lastname: Oberton
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Rushing
authors.forename: Sheryl L
authors.initials: SL
authors.lastname: Santoro
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology / Q000821:virology; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D007202:Indicators and Reagents; D018942:Macrolides; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D010326:Pasteurella Infections / Q000188:drug therapy / Q000382:microbiology; D016979:Pasteurella multocida / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D018942:Macrolides