Quinolone Antibacterials: Preparation and Activity of Bridged Bicyclic Analogues of the C7-Piperazine

Article abstract of DOI:10.1021/jm00106a029

A series of quinolone and naphthyridine antibacterial agents possessing as the C7-heterocycle bicyclic 2,5-diazabicycloalkanes, 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 Gramm-negative and Gramm-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.