Synthesis of possible metabolites of 1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl)- 4-oxo-3-quinolinecarboxylic acid (Grepafloxacin, OPC-17116).
Grepafloxacin (1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl )-4-oxo-3-quinoline-carboxylic acid, OPC-17116) (1) exhibits potent and broad-spectrum in vitro and in vivo antibacterial activity. In order to identify the structures of the metabolites of grepafloxacin, 17 possible metabolites were prepared. Among them, 6 compounds were found to be actual metabolites (2a, b, 4a, b and 6a, b) of grepafloxacin in rats, dogs and/or humans. The antibacterial activities of these metabolites were found to be weaker than that of grepafloxacin.
Morita
S
S
Tokushima Research Institute, Otsuka Pharmaceutical Co., Japan.
Otsubo
K
K
Matsubara
J
J
Ohtani
T
T
Kawano
Y
Y
Ohmori
K
K
Ohguro
K
K
Uchida
M
M
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001711:Biotransformation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004285:Dogs; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; C075375:grepafloxacin