Synthesis of antimicrobial agents. 5. In vivo metabolism of 7-(4-hydroxypiperazin-1-yl)quinolones.
A series of novel pyridone carboxylic acids having a 4-hydroxypiperazin-1-yl, a 4-hydroxy-3-methylpiperazin-1-yl, and a 4-hydroxy-3,5-dimethylpiperazin-1-yl group was prepared, and their metabolism to corresponding piperazinyl derivatives after oral administration to mice and rats was studied. This reductive metabolism appeared to be more extensive in mice than in rats. Moreover, the introduction of a methyl group into the alpha-position of the 4-hydroxy group depressed the metabolism in both species.
Uno
T
T
Pharmaceuticals Research Center, Kanebo Ltd., Osaka, Japan.
Okuno
T
T
Kawakami
K
K
Sakamoto
F
F
Tsukamoto
G
G
D042462:4-Quinolones; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis*; D051379:Mice; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship
D042462:4-Quinolones; D000890:Anti-Infective Agents; D010879:Piperazines