Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates.
A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibacterial spectrum derived from both cephalosporin-like and quinolone-like activities, suggesting a dual mode of action. Studies to elucidate details of the mechanism of action have been inconclusive. Ciprofloxacin liberated as a consequence of bacterial enzyme-mediated reactions may contribute to the second mode of action, although some evidence indicates that the intact carbamate-linked bifunctional molecules may possess intrinsically both beta-lactam and quinolone activities.
Albrecht
H A
HA
Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Beskid
G
G
Christenson
J G
JG
Georgopapadakou
N H
NH
Keith
D D
DD
Konzelmann
F M
FM
Pruess
D L
DL
Rossman
P L
PL
Wei
C C
CC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology; D002511:Cephalosporins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000900:Anti-Bacterial Agents; D002219:Carbamates; D002511:Cephalosporins; D002939:Ciprofloxacin; D002439:Cefotaxime