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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.

Irradiation of quinoline and 8-methylquinoline in acidic ethanol yielded the 2-and 4-ethylquinolines. Irradiation in 95% ethanol yielded the 2-a-hydroxyethylquinolines together with the corresponding 1,2,3,4-tetrahydroquinolines. Irradiation of quinoline in f-butyl alcohol yielded 2-(2-hydroxy-2-methylpropyl)quinoline. Photoalkylation did not proceed in 2-propanol but instead a low yield of a reduced quinoline dimer occurred. If 2-substituted quinolines containing a -hydrogen were irradiated in inert solvents, an elimination corresponding to ketone type II cleavage would occur with quantum yields varying from 0.014 to 0.29 depending upon the structure of the starting quinoline. This reaction was shown (by quenching studies) to proceed through an excited singlet, probably of n-* configuration. The photoelimination had a McLafferty rearrangement counterpart in the electron-impact fragmentations of the 2-substituted quinolines.

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.