Discovery and structure-activity relationship of a series of 1-carba-1-dethiacephems exhibiting activity against methicillin-resistant Staphylococcus aureus.
The synthesis and antimicrobial activity of several new 1-carba-1-dethiacephalosporins is described. The discovery of unique activity of some of the analogues against methicillin-resistant Staphylococcus aureus led to the development of a structure-activity relationship designed to optimize this activity. The results of this investigation along with the pharmacokinetic characteristics of select compounds are described.
Ternansky
R J
RJ
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Draheim
S E
SE
Pike
A J
AJ
Bell
F W
FW
West
S J
SJ
Jordan
C L
CL
Wu
C Y
CY
Preston
D A
DA
Albron
W
W
Kasher
J S
JS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D002511:Cephalosporins