Synthesis of novel 5-fluoro analogs of norfloxacin and ciprofloxacin

• Published in: Journal of medicinal chemistry Vol. 32; no. 6; pp. 1313 - 1318
• Main Authors: Moran, Daniel B, Ziegler, Carl B, Dunne, Theresa S, Kuck, Nydia A, Lin, Yang I
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.06.1989
• Subjects: Animals; Chemical Phenomena; Chemistry; Ciprofloxacin - analogs & derivatives; Ciprofloxacin - chemical synthesis; Ciprofloxacin - pharmacology; Enterobacter - drug effects; Enterococcus faecalis - drug effects; Escherichia coli - drug effects; Escherichia coli Infections - drug therapy; Exact sciences and technology; Klebsiella pneumoniae - drug effects; Magnetic Resonance Spectroscopy; Mice; Microbial Sensitivity Tests; Molecular Structure; Norfloxacin - analogs & derivatives; Norfloxacin - chemical synthesis; Norfloxacin - pharmacology; Organic chemistry; Pseudomonas aeruginosa - drug effects; Serratia marcescens - drug effects; Staphylococcal Infections - drug therapy; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Fluorine Organic compounds
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00126a028

A series of polyfluoro-3-quinolonecarboxylic acids have been synthesized and their in vitro antibacterial activity evaluated. The desired 7-(substituted amino) derivatives were prepared from the 5,6,7,8-tetrafluoroquinolone acids. Conversely, amine displacement occurred primarily at the 5-position when the ester was used. Structure-activity studies indicated that the antibacterial activity was greatest when the N-1 substituent was cyclopropyl and the 7-substituent was 4-methyl-1-piperazinyl. All 5-(substituted amino) derivatives showed poor in vitro activity.