Document Report Card

ID: ALA1128719

Journal: J Med Chem

Title: The synthesis, structure-activity, and structure-side effect relationships of a series of 8-alkoxy- and 5-amino-8-alkoxyquinolone antibacterial agents.

Authors: Sanchez JP, Gogliotti RD, Domagala JM, Gracheck SJ, Huband MD, Sesnie JA, Cohen MA, Shapiro MA.

Abstract: A series of 1-cyclopropyl-6-fluoro-8-alkoxy (8-methyoxy and 8-ethoxy)-quionoline-3-carboxylic acids and 1-cyclopropyl-5-amino-6-fluoro-8-alkoxyquinoline-3-carboxylic acids has been prepared and evaluated for antibacterial activity. In addition, they were also compared to quinolones with classic substitution at C8 (H, F, Cl) and the naphthyridine nucleus in a phototoxicity and mammalian cell cytotoxicity assay. The series of 8-methoxyquinolones had antibacterial activity against Gram-positive, Gram-negative, and anaerobic bacteria equivalent to the most active 8-substituted compounds (8-F and 8-Cl). There was also a concomitant reduction in several of the potential side effects (i.e., phototoxicity and clonogenicity) compared to the most active quinolones with classic substitution at C-8. The 8-ethoxy derivatives had an even better safety profile but were significantly less active (2-3 dilutions) in the antibacterial assay.

CiteXplore: 7473575

DOI: 10.1021/jm00022a013