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

J Med Chem. 1988 Jan;31(1):221-5. doi: 10.1021/jm00396a035.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • 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

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Indicators and Reagents
  • Pharmaceutical Preparations
  • Prodrugs
  • 1-ethyl-6-fluoro-3-formyl-1,4-dihydro-4-oxo-7-piperazinylquinoline
  • 1-cyclopropyl-6-fluoro-3-formyl-1,4-dihydro-4-oxo-7-piperazinylquinoline
  • 1-ethyl-6-fluoro-3-formyl-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxoquinoline
  • Pefloxacin
  • Ciprofloxacin
  • Norfloxacin