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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.

Reaction of l,2,3,4-Tetrahydro-2-methylisoquinoline with BrCN.-To a solution of BrCN (7.50 g, 70.80 mmol) in 50 ml of anhydrous C61I6, a solution of 1,2,3,4-ietrahydro-2-methylisoquinoliiie (21) (6.00 g, 40.75 mmol) in 100 ml of anhydrous C»II, was added slowly over a period of 2 hr. Essentially the same procedure was previously employed to obtain N-CN rampound was utilized to give a colorless viscous residue which crystallized into fine needles, 22 (3.52 g, 22.25 mmol, 54.(50r, !, mp 45 -44

Durch Umsetzung der Verbindungen (I) mit den 4,4‐disubstituierten Piperidinen (II) oder durch Reaktion von (IV) mit den Grignardverbindungen (V) wurde eine Reihe von Phenothiazinen, Iminodibenzylen, Iminostilbenen und Aminoacridanen (III) und (VI) dargestellt.

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