Studies on prodrugs. 7. Synthesis and antimicrobial activity of 3-formylquinolone derivatives.
Several 3-formylquinolone derivatives (8a-c) were synthesized to assay the antibacterial activity both in vitro and in vivo. In vitro, all of the compounds 8a-c showed lower activity than that of the corresponding 3-carboxyl compounds 1a-c, and in vivo, they showed higher activity than that of compounds 1a-c. After oral administration of 3-formyl compounds 8a-c to mice, the compounds were rapidly metabolized into 3-carboxyl compounds 1a-c. In particular, the 3-formyl derivative (8a) of norfloxacin (NFLX, 1a) gave a 2-fold higher serum level than that of NFLX and functioned as a prodrug of NFLX.
Kondo
H
H
Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
Sakamoto
F
F
Kawakami
K
K
Tsukamoto
G
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001682:Biological Availability; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D004927:Escherichia coli Infections / Q000188:drug therapy; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007202:Indicators and Reagents; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D015366:Pefloxacin / Q000031:analogs & derivatives*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*; D011355:Prodrugs / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D011355:Prodrugs; C054519:1-ethyl-6-fluoro-3-formyl-1,4-dihydro-4-oxo-7-piperazinylquinoline; C054520:1-cyclopropyl-6-fluoro-3-formyl-1,4-dihydro-4-oxo-7-piperazinylquinoline; C054521:1-ethyl-6-fluoro-3-formyl-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline; D015366:Pefloxacin; D002939:Ciprofloxacin; D009643:Norfloxacin