Quinolone antibacterials: preparation and activity of bridged bicyclic analogues of the C7-piperazine.
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.
Kiely
J S
JS
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Hutt
M P
MP
Culbertson
T P
TP
Bucsh
R A
RA
Worth
D F
DF
Lesheski
L E
LE
Gogliotti
R D
RD
Sesnie
J C
JC
Solomon
M
M
Mich
T F
TF
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
D042462:4-Quinolones; D000890:Anti-Infective Agents; D001643:Bridged Bicyclo Compounds; D010879:Piperazines