Synthesis of antimicrobial agents. 1. Syntheses and antibacterial activities of 7-(azole substituted)quinolones

Abstract

A series of 6-fluoro- and 6,8-difluoro-7-(azole substituted)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared. Structure-activity relationship studies indicated that the antibacterial potency was better when the 6,8-substituents were fluorine atoms and the 7-substituent was either 1-imidazolyl, 20, or 4-methyl-1-imidazolyl, 25. From the results of studies on pharmacokinetic profile and toxicity, 20 and 25 were found to possess excellent antibacterial activities and to show high blood levels after oral administration to mice with low toxicity.

Quinolone–Triazole Hybrids and their Biological Activities

“…Several series of other quinolone–triazole hybrids were screened for their antibacterial activities by different groups , in spite of most of them showed poor to moderate activities, the enriched SAR pave the way to find more potent antibacterial candidates.…”

Quinolone Antibacterials

“…For example, the pyrrolyl radical is introduced by condensation of 7-amino-quinolones with 2,5-dimethoxy- tetrahydrofuran (UNO et al 1987;ESTEVE SOLER 1983/1984PETERSEN et al 1985), the 1,2,4-triazol-4-yl radical is introduced by reaction with N, Ndimethylformamidazine (UNO et al 1987) and the pyrazolyl radical is introduced by condensation of 7-hydrazinoquinolones with 1,1,3,3tetramethoxypropane (PETERSEN et al 1985). For example, the pyrrolyl radical is introduced by condensation of 7-amino-quinolones with 2,5-dimethoxy- tetrahydrofuran (UNO et al 1987;ESTEVE SOLER 1983/1984PETERSEN et al 1985), the 1,2,4-triazol-4-yl radical is introduced by reaction with N, Ndimethylformamidazine (UNO et al 1987) and the pyrazolyl radical is introduced by condensation of 7-hydrazinoquinolones with 1,1,3,3tetramethoxypropane (PETERSEN et al 1985).…”

“…In contrast to the substitution reactions described for the 8-position, only the 6-dimethylamino derivative is isolated after reaction of a 6,8difluoroquinolone with dimethylamine as the nucleophile (22% yield; UNO et al 1987). 8-Dimethylamino substitution was achieved by reductively methylating an 8-aminoquinolone using formaldehyde, formic acid and sodium acetate (MAsuzAwA et al 1986b).…”