Synthesis of novel 5-fluoro analogues of norfloxacin and ciprofloxacin.
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.
Moran
D B
DB
American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.
Ziegler
C B
CB
Dunne
T S
TS
Kuck
N A
NA
Lin
Y I
YI
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004754:Enterobacter / Q000187:drug effects; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D007711:Klebsiella pneumoniae / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012706:Serratia marcescens / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D002939:Ciprofloxacin; D009643:Norfloxacin