Studies on 2(1H)-Quinolinone Derivatives as Neuroleptic Agents. I. : Synthesis and Biological Activities of (4-Phenyl-1-piperazinyl)-propoxy-2(1H)-quinolinone Derivatives

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With the aim of developing a novel neuroleptic drug, a series of ω-(4-phenyl-1-piperazinyl)-alkoxy-2(1H)-quinolinone derivatives have been synthesized and tested for anti-methamphetamine and anti-epinephrine activities. Most of the derivatives were found to possess a potent anti-methamphetamine activity in the jumping behavior test on mice treated with 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) and methamphetamine, or in the lethality test with methamphetamine-treated mice. They also showed relatively high anti-epinephrine potency depending on the nature or number of substituents on the phenyl group in the 4-phenyl-1-piperazinyl moiety; some of these compounds induced only weak catalepsy in mice. Among them, 7-{3-[4-(2,3-dimethylphenyl)-1-piperazinyl]propoxy}-2(1H)-quinolinone (OPC-4392), which was suggested to be a dopamine autoreceptor agonist, was selected for further investigations. The structure-activity relationships are also discussed.
社団法人日本薬学会の論文
1988-11-25