Synthesis and activity of a novel class of tribasic macrocyclic antibiotics: the triamilides.
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.
Letavic
Michael A
MA
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. michael_a_letavic@groton.pfizer.com
Bronk
Brian S
BS
Bertsche
Camilla D
CD
Casavant
Jeffrey M
JM
Cheng
Hengmiao
H
Daniel
Kirsten L
KL
George
David M
DM
Hayashi
Shigeru F
SF
Kamicker
Barbara J
BJ
Kolosko
Nicole L
NL
Norcia
Laura J L
LJ
Oberton
Vanessa D
VD
Rushing
Margaret A
MA
Santoro
Sheryl L
SL
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
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D018942:Macrolides