Cephalosporin 3'-quinolone esters with a dual mode of action.
According to the generally accepted mechanism by which bacterial enzymes react with cephalosporins, opening of the beta-lactam ring can lead to the expulsion of a 3'-substituent. A series of dual-action cephalosporins was prepared in which antibacterial quinolones were linked to the cephalosporin 3'-position through an ester bond in the expectation that, in addition to exerting their own beta-lactam activity, these cephalosporins would act as prodrugs for the second antibacterial agent. Compared to parent cephalosporins in which the 3'-substituent was acetoxy, the bifunctional cephalosporins exhibited a broadened antibacterial spectrum, suggesting that a dual mode of action may indeed be operative.
Albrecht
H A
HA
Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Beskid
G
G
Chan
K K
KK
Christenson
J G
JG
Cleeland
R
R
Deitcher
K H
KH
Georgopapadakou
N H
NH
Keith
D D
DD
Pruess
D L
DL
Sepinwall
J
J
D000818:Animals; D000890:Anti-Infective Agents; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000494:pharmacology; D004754:Enterobacter / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D016576:Fleroxacin / Q000031:analogs & derivatives*; D024841:Fluoroquinolones; D006868:Hydrolysis; D051379:Mice; D015394:Molecular Structure; D011008:Pneumococcal Infections / Q000188:drug therapy; D011355:Prodrugs; D015363:Quinolones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D011355:Prodrugs; D015363:Quinolones; C060441:Ro-23-9424; D002939:Ciprofloxacin; D002439:Cefotaxime; D016576:Fleroxacin