title: Dual-action cephalosporins incorporating a 3'-tertiary-amine-linked quinolone.
abstract: 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.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Incorporated, Nutley, New Jersey 07110.
authors.forename: H A
authors.initials: HA
authors.lastname: Albrecht
authors.forename: G
authors.initials: G
authors.lastname: Beskid
authors.forename: J G
authors.initials: JG
authors.lastname: Christenson
authors.forename: K H
authors.initials: KH
authors.lastname: Deitcher
authors.forename: N H
authors.initials: NH
authors.lastname: Georgopapadakou
authors.forename: D D
authors.initials: DD
authors.lastname: Keith
authors.forename: F M
authors.initials: FM
authors.lastname: Konzelmann
authors.forename: D L
authors.initials: DL
authors.lastname: Pruess
authors.forename: C C
authors.initials: CC
authors.lastname: Wei
mesh_terms: 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
chemical_list: D002511:Cephalosporins; D011804:Quinolines; D002939:Ciprofloxacin; C037219:quinoline; D001618:beta-Lactamases; D009584:Nitrogen