Synthesis and biological evaluation of a series of parenteral 3'-quaternary ammonium cephalosporins.
The preparation and biological evaluation of a series of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoximinoacetamido]cep halosporins, substituted at the 3'-position with monocyclic or bicyclic nitrogen-containing heterocycles are described. The resulting family of parenteral compounds displays a broad spectrum of antibacterial activity. Some compounds exhibit a similar level of Gram-negative activity to that of the "third-generation" cephalosporins with increased staphylococcal activity. The in vitro and in vivo antimicrobial activity, structure-activity relationships, beta-lactamase stability, and in vitro and in vivo pharmacological evaluations are presented.
Brown
R F
RF
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285.
Kinnick
M D
MD
Morin
J M
JM
Vasileff
R T
RT
Counter
F T
FT
Davidson
E O
EO
Ensminger
P W
PW
Eudaly
J A
JA
Kasher
J S
JS
Katner
A S
AS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002511:Cephalosporins / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010276:Parasympatholytics / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D012706:Serratia marcescens / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism
D002511:Cephalosporins; D010276:Parasympatholytics; D001618:beta-Lactamases