title: New 8-(trifluoromethyl)-substituted quinolones. The benefits of the 8-fluoro group with reduced phototoxic risk.
abstract: A series of 8-(trifluoromethyl)-substituted quinolones has been prepared and evaluated for in vitro and in vivo antibacterial activity, and phototolerance in a mouse phototolerance assay. These analogues were compared to the corresponding series of 6,8-difluoro- and 6-fluoro-8H-quinolones (ciprofloxacin type). Although their in vitro antibacterial activities are less than the 6,8-difluoro analogues, the 8-(trifluoromethyl)quinolones are generally equivalent to their 8H analogues. In vivo, they are comparable to the 6,8-difluoro series and show up to 10-fold improvement in efficacy when compared to their ciprofloxacin counterparts vs Streptococcus pyogenes and Streptococcus pneumonia. In the phototolerance model, the 8-(trifluoromethyl)quinolones are comparable to the 8H-quinolones. Both of these series display much higher no effect doses (greater tolerance) than the corresponding 6,8-difluoroquinolones.
authors.affiliation: Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48106.
authors.forename: J P
authors.initials: JP
authors.lastname: Sanchez
authors.forename: A J
authors.initials: AJ
authors.lastname: Bridges
authors.forename: R
authors.initials: R
authors.lastname: Bucsh
authors.forename: J M
authors.initials: JM
authors.lastname: Domagala
authors.forename: R D
authors.initials: RD
authors.lastname: Gogliotti
authors.forename: S E
authors.initials: SE
authors.lastname: Hagen
authors.forename: C L
authors.initials: CL
authors.lastname: Heifetz
authors.forename: E T
authors.initials: ET
authors.lastname: Joannides
authors.forename: J C
authors.initials: JC
authors.lastname: Sesnie
authors.forename: M A
authors.initials: MA
authors.lastname: Shapiro
mesh_terms: D042462:4-Quinolones; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity*; D001424:Bacterial Infections / Q000188:drug therapy; D005260:Female; D007279:Injections, Subcutaneous; D051379:Mice; D008826:Microbial Sensitivity Tests; D010787:Photosensitivity Disorders / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents