title: Synthesis and structure-activity relationships of new 7-[3-(fluoromethyl)piperazinyl]- and -(fluorohomopiperazinyl)quinolone antibacterials.
abstract: Some novel 6-fluoro-7-substituted-1,4-dihydro-4-oxoquinoline-3-carboxylic acids have been prepared. At the N-1 position "standard" substitution was employed with the ethyl, cyclopropyl, and p-fluorophenyl groups being used. At C-7 the introduction of some novel piperazines was made. Most notably, 2-(fluoromethyl)piperazine (10) and hexahydro-6-fluoro-1H-1,4-diazepine (16, fluorohomopiperazine) at the quinolone C-7 position produced products with similar in vitro antibacterial activity as the ciprofloxacin reference. The in vivo efficacy of 1-cyclopropyl-6-fluoro-7-[3-(fluoromethyl)piperazinyl]-1,4-dihydro-4- oxoquinoline-3-carboxylic acid (20) was excellent with better oral absorption than ciprofloxacin (2).
authors.affiliation: American Cyanamid Company, Medical Research Division, Lederle Laboratories, Pearl River, New York 10965.
authors.forename: C B
authors.initials: CB
authors.lastname: Ziegler
authors.forename: P
authors.initials: P
authors.lastname: Bitha
authors.forename: N A
authors.initials: NA
authors.lastname: Kuck
authors.forename: T J
authors.initials: TJ
authors.lastname: Fenton
authors.forename: P J
authors.initials: PJ
authors.lastname: Petersen
authors.forename: Y I
authors.initials: YI
authors.lastname: Lin
mesh_terms: D042462:4-Quinolones; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004754:Enterobacter / Q000187:drug effects; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D005260:Female; D051379:Mice; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D011511:Proteus / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D042462:4-Quinolones; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010879:Piperazines