THE SYNTHESIS, STRUCTURE-ACTIVITY, AND STRUCTURE-SIDE EFFECT RELATIONSHIPS OF A SERIES OF 8-ALKOXYQUINOLONE AND 5-AMINO-8-ALKOXYQUINOLONE ANTIBACTERIAL AGENTS

A series of 1-cyclopropyl-6-fluoro-8-alkoxy (8-methoxy and 8-ethoxy)-q uionoline-3-carboxylic acids and yl-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 clas sic substitution at C-8 (H, F, Cl) and the naphthyridine nucleus in a phototoxicity and mammalian cell cytotoxicity assay. The series of 8-m ethoxyquinolones had antibacterial activity against Gram-positive, Gra m-negative, and anaerobic bacteria equivalent to the most active 8-sub stituted compounds (8-F and 8-Cl). There was also a concomitant reduct ion in several of the potential side effects (i.e., phototoxicity and clonogenicity) compared to the most active quinolones with classic sub stitution at C-8. The 8-ethoxy derivatives had an even better safety p rofile but were significantly less active (2-3 dilutions) in the antib acterial assay.