L. Jian-qi
2011
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0
Influential Citations
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Quality indicators
Journal
Chinese Journal of Medicinal Chemistry
Abstract
7-Aminoalkyloxy-3,4-dihydroquinolin-2(1H)-ones have D2 receptor affinity,and aromatic heterocyclic piperidines or piperazines have 5-HT2A and 5-HT1A affinity,These two fragments were introduced to one structure,with a public nitrogen atom.Eleven new 3,4-dihydroquinolin-2(1H)-one derivatives were designed and synthesized.This new serial compounds were prepared by the following method:7-hydroxyl-3,4-dihydroquinolin-2(1H)-one was reacted with dihalides as O-alkylation reaction to yield Ⅲ,and then the target compounds were prepared by Ⅲ and corresponding piperidine derivatives(Ⅰ1-Ⅰ11).The in vitro activities to D2,5-HT2A,5-HT1A receptors were tested for target compounds,their binding affinities to D2 and 5-HT1A are about 1-100 nmol · L-1,and to 5-HT2A are about 1-10 nmol · L-1.Their in vivo activity of apomorphine-induced stereotype in mice for representative compound Ⅰ7 were also tested,and it showed high inhibitory rate(70.23%) at 0.35 mg · kg-1(p.o.).Preliminary SAR indicates:The chain in the middle with three or four carbon atoms gives better activities to D2 and 5-HT2A,3-(piperazin-1-yl)benzo[d]isothiazole is more beneficial for 5-HT1A activity than 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole.