title: Quinolone antibacterials: preparation and activity of bridged bicyclic analogues of the C7-piperazine.
abstract: A series of quinolone and naphthyridine antibacterial agents possessing as the C7-heterocycle bicyclic 2,5-diazabicyclo[n.2.m]alkanes, where n = 2, 3 and m = 1, 2, and a series including 4-aminopiperidine and 3-amino-8-azabicyclo[3.2.1]octanes have been prepared and evaluated in vitro and in vivo for antibacterial activity against a variety of Gram-negative and Gram-positive organisms. These compounds were also tested against the target enzyme bacterial DNA gyrase. All the examples investigated are nearly equipotent with the parent 7-piperazinyl analogues. Only endo-7-(3-amino-8-azabicyclo[3.2.1]oct-8-yl)-1-cyclopropyl-6,8-difluoro- 1,4- dihydro-4-oxo-3-quinolinecarboxylic acid displays activity that surpasses that of the piperazine parent.
authors.affiliation: Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
authors.forename: J S
authors.initials: JS
authors.lastname: Kiely
authors.forename: M P
authors.initials: MP
authors.lastname: Hutt
authors.forename: T P
authors.initials: TP
authors.lastname: Culbertson
authors.forename: R A
authors.initials: RA
authors.lastname: Bucsh
authors.forename: D F
authors.initials: DF
authors.lastname: Worth
authors.forename: L E
authors.initials: LE
authors.lastname: Lesheski
authors.forename: R D
authors.initials: RD
authors.lastname: Gogliotti
authors.forename: J C
authors.initials: JC
authors.lastname: Sesnie
authors.forename: M
authors.initials: M
authors.lastname: Solomon
authors.forename: T F
authors.initials: TF
authors.lastname: Mich
mesh_terms: D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D042462:4-Quinolones; D000890:Anti-Infective Agents; D001643:Bridged Bicyclo Compounds; D010879:Piperazines