Synthesis and bacterial DNA gyrase inhibitory properties of a spirocyclopropylquinolone derivative.
A novel conformationally restricted 1-cyclopropylquinolone (1) that incorporates structural features of both ofloxacin and ciprofloxacin has been prepared. Compound 1 was found to be a DNA gyrase inhibitor having potency similar to ofloxacin but less than ciprofloxacin. The cellular inhibitory and in vivo antibacterial potencies of 1 were found to be less than those of the two reference agents.
Wentland
M P
MP
Department of Medicinal Chemistry, Sterling-Winthrop Research Institute, Rensselaer, New York 12144.
Perni
R B
RB
Dorff
P H
PH
Rake
J B
JB
D000818:Animals; D001439:Bacteroides / Q000201:enzymology; D055598:Chemical Phenomena; D002621:Chemistry; D002939:Ciprofloxacin / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D051379:Mice; D015242:Ofloxacin; D010078:Oxazines / Q000138:chemical synthesis / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D013211:Staphylococcus aureus / Q000201:enzymology; D013291:Streptococcus / Q000201:enzymology; D059005:Topoisomerase II Inhibitors
D010078:Oxazines; D059005:Topoisomerase II Inhibitors; C056975:9'-fluoro-10'-(4-methyl-1-piperazinyl)-7'-oxospiro(cyclopropane-1,3'(2'H)-(7H)pyrido(1,2,3-de)(1,4)benzoxazine)-6'-carboxylic acid; D002939:Ciprofloxacin; D015242:Ofloxacin