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.

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Quinolone Antimicrobial Agents, e.g. (I), Substituted with Morpholines at the 7-Position.Syntheses and Structure-Activity Relationships.--(ARAKI, K.; KURODA, T.; UEMORI, S.; MORIGUCHI, A.; IKEDA, Y.; HIRAYAMA, F.; YOKOYAMA, Y.; IWAO, E.; YAKUSHIJI, T.; J. Med.

Synthesisand Structure-Activity Relationships of 7-(2-Aminoalkyl)morpholinoquinolones as anti-Helicobacter pylori Agents. -A series of new 7-aminoalkylmorpholinoquinolones [cf. (V), (VI)] are synthesized and evaluated for their in vitro and in vivo anti-H. pylori activities. The enantiopure derivative (V) (Y-34867) appears to be the most potent compound among the quinolones tested. -(SAKURAI, N.; SANO, M.; HIRAYAMA, F.; KURODA, T.; UEMORI, S.; MORIGUCHI, A.; YAMAMOTO, K.; IKEDA, Y.; KAWAKITA, T.; Bioorg. Med.