ABSTRACT
A series of the titled compounds was synthesized and tested for anti-Helicobacter pylori activities. We discovered Y-34867 having the most potent activity against Helicobacter pylori among the quinolones tested along with high photostability. Furthermore, Y-34867 showed an excellent therapeutic effect in the experimental Helicobacter pylori infected Mongolian gerbil model.
Subject(s)
4-Quinolones , Anti-Infective Agents/chemical synthesis , Fluoroquinolones , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Quinolones/chemistry , Quinolones/chemical synthesis , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Drug Stability , Gerbillinae , Indicators and Reagents , Microbial Sensitivity Tests , Molecular Structure , Naphthyridines/pharmacology , Ofloxacin/pharmacology , Quinolones/pharmacology , Quinolones/therapeutic use , Solutions , Structure-Activity Relationship , Ultraviolet RaysABSTRACT
A series of novel 7-substituted 1-cyclopropyl-6,8-difluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids have been prepared and tested for antibacterial activities and for convulsive activities in combination with nonsteroidal antiinflammatory drug. Structure-activity relationships revealed that 7-(2-(aminomethyl)morpholino) derivative 28 had a better Gram-positive activity than the reference quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin. Its Gram-negative activity was equipotent with those of norfloxacin and ofloxacin but was inferior to that of ciprofloxacin. In mouse systemic infection models, 28 showed an excellent therapeutic efficacy which might result from the potent antibacterial activity and suitable physicochemical properties. Convulsive activities of 7-morpholino derivatives in combination with nonsteroidal antiinflammatory drug fenbufen or its metabolite biphenylacetic acid markedly diminished as compared to those of 7-piperazino derivatives in the electrophysiological, biochemical, and behavioral experiments. These results suggest that 28 (Y-26611) is a novel quinolone with reduced neurotoxic excitatory adverse reaction.
