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Published on: April 18, 2019
Cephalosporin 3'-quinolone esters with a dual mode of action
H A Albrecht1, G Beskid, K K Chan
1Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Abstract:
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.
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