Pyridonecarboxylic acids as antibacterial agents. VIII. Synthesis and structure-activity relationship of 7-(1-aminocyclopropyl)-4-oxo-1,8-naphthyridine-3-carboxylic acids and 7-(1-aminocyclopropyl)-4-oxoquinoline-3-carboxylic acids.
4-Oxo-1,8-naphthyridine- and 4-oxoquinoline-3-carboxylic acids (2a, b and 3a-1) possessing a 1-amino-cyclopropyl group at the 7-position have been synthesized and evaluated for in vitro antibacterial activities. The three quinolones (3d, h, i) exhibited potent antibacterial activities against both gram-positive and gram-negative bacteria, which are comparable to those of ciprofloxacin (CPFX) and ofloxacin (OFLX). Among the three compounds, the best pharmacological and pharmacokinetic profile was obtained with 3i, an OFLX analogue, which was considerably less toxic than three reference quinolones (1, CPFX and OFLX).
Todo
Y
Y
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Nitta
J
J
Miyajima
M
M
Fukuoka
Y
Y
Yamashiro
Y
Y
Nishida
N
N
Saikawa
I
I
Narita
H
H
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D051379:Mice; D012640:Seizures / Q000139:chemically induced; D013329:Structure-Activity Relationship
D042462:4-Quinolones; D000890:Anti-Infective Agents