Pyridonecarboxylic acids as antibacterial agents. VI. Synthesis and structure-activity relationship of 7-(alkyl, cycloalkyl, and vinyl)-1-cyclopropyl-6-fluoro-4-quinolone-3-carboxylic acids.
The title compounds (1a-i) have been synthesized starting with ethyl 1-cyclopropyl-6,7-difluoro-4-quinolone-3-carboxylate (2). The 7-cyclopropyl and 7-vinyl derivative (1e and 1i) exhibited potent in vitro antibacterial activities against both gram-positive and gram-negative bacteria, being equipotent with ciprofloxacin (CPFX) except for the activity against Pseudomonas aeruginosa. The two compounds were significantly less toxic than CPFX in terms of convulsion-induction as determined by intracerebral administration to mice, but showed lower urinary recoveries on intravenous administration.
Todo
Y
Y
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Takagi
H
H
Iino
F
F
Fukuoka
Y
Y
Ikeda
Y
Y
Tanaka
K
K
Saikawa
I
I
Narita
H
H
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012640:Seizures / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D042462:4-Quinolones; D000890:Anti-Infective Agents