Dual-action cephalosporins incorporating a 3'-tertiary-amine-linked quinolone.
We have previously reported that linking quinolones to the cephalosporin 3'-position through an ester bond, a carbamate function, or a bond through a quaternary nitrogen produced cephalosporins with a dual mode of antibacterial action. We now describe a new class of dual-action cephalosporins, with greater chemical stability than those previously reported, in which the basic nitrogen of ciprofloxacin is bonded directly to the 3'-cephalosporin position, i.e., the two moieties are linked through a tertiary amine function. These compounds have demonstrated potent activity against a broad spectrum of Gram-positive and Gram-negative bacteria, including beta-lactam-resistant strains.
Albrecht
H A
HA
Roche Research Center, Hoffmann-La Roche Incorporated, Nutley, New Jersey 07110.
Beskid
G
G
Christenson
J G
JG
Deitcher
K H
KH
Georgopapadakou
N H
NH
Keith
D D
DD
Konzelmann
F M
FM
Pruess
D L
DL
Wei
C C
CC
D002511:Cephalosporins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000737:chemistry; D004352:Drug Resistance, Microbial; D004355:Drug Stability; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism
D002511:Cephalosporins; D011804:Quinolines; D002939:Ciprofloxacin; C037219:quinoline; D001618:beta-Lactamases; D009584:Nitrogen