title: Synthesis and antibacterial activity of a new series of tetracyclic pyridone carboxylic acids.
abstract: A series of novel tetracyclic pyridone carboxylic acids replacing the 10-position oxygen atom of 9,1-(epoxymethano)-7-fluoro-8-(4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo [3,2-alpha]quinoline-4-carboxylic acid by imino groups (NR; R = Me, Et, c-Pr, allyl, Ph, benzyl), a sulfur atom, or a carbonyl group was prepared and evaluated for antibacterial activity and inhibitory activity on DNA gyrase isolated from E. coli KL-16. The in vitro antibacterial potency and DNA gyrase inhibitory activity were found to be in the following order: NMe > or = O > S >> C = O. Moreover, a methyl group was the optimal alkyl substituent at the 10-position nitrogen atom for antibacterial activity and for DNA gyrase inhibitory activity. 7-Fluoro-9,1-[(N-methylimino)methano]-8- (4-methyl-1-piperazinyl)-5-oxo-5H-thiazolo[3,2-alpha]quinoline-4-carboxy lic acid (10-NCH3) showed potent in vivo antibacterial activity.
authors.affiliation: New Drug Research Laboratories, Kanebo, Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Jinbo
authors.forename: H
authors.initials: H
authors.lastname: Kondo
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Taguchi
authors.forename: H
authors.initials: H
authors.lastname: Tsujishita
authors.forename: Y
authors.initials: Y
authors.lastname: Kotera
authors.forename: F
authors.initials: F
authors.lastname: Sakamoto
authors.forename: G
authors.initials: G
authors.lastname: Tsukamoto
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents; D001424:Bacterial Infections / Q000188:drug therapy; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010879:Piperazines; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D015363:Quinolones; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors
chemical_list: D000890:Anti-Infective Agents; D002264:Carboxylic Acids; D024841:Fluoroquinolones; D010879:Piperazines; D011728:Pyridones; D011804:Quinolines; D015363:Quinolones; D013844:Thiazoles; D059005:Topoisomerase II Inhibitors; C074008:tetracyclic quinolone No. 5290