Studies on prodrugs. 7. Synthesis and antimicrobial activity of 3-formylquinolone derivatives

• Published in: Journal of medicinal chemistry 1988-01, Vol.31 (1), p.221-225
• Main Authors: Kondo, Hirosato, Sakamoto, Fumio, Kawakami, Kiyotaka, Tsukamoto, Goro
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Biological Availability; Ciprofloxacin - analogs & derivatives; Ciprofloxacin - chemical synthesis; Ciprofloxacin - pharmacology; Ciprofloxacin - therapeutic use; Escherichia coli Infections - drug therapy; Fluoroquinolones; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Indicators and Reagents; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Norfloxacin - analogs & derivatives; Norfloxacin - chemical synthesis; Norfloxacin - pharmacology; Norfloxacin - therapeutic use; Pefloxacin - analogs & derivatives; Pharmaceutical Preparations - chemical synthesis; Prodrugs - chemical synthesis; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00396a035

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.