Design,synthesis and anti-schizophrenia activity of 3,4-dihydroquinolin-2(1H)-one derivatives

	Design,synthesis and anti-schizophrenia activity of 3,4-dihydroquinolin-2(1H)-one derivatives
	GU Shunlin 1; MA Zhilong 1; LI Yali 1; YU Leiping 2; LI Jianqi 1
刊名	Chinese Journal of Medicinal Chemistry
	2011
卷号	21 期号:2 页码:81-87
关键词	3,4-dihydroquinolin-2(1H)-one anti-schizophrenia synthesis
ISSN号	1005-0108
其他题名	3,4-二氢喹啉-2(1H)-酮衍生物的设计合成及抗精神分裂活性研究
文献子类	Article
英文摘要	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.
资助项目	国家十一五重大新药创制资助项目[00000000]
WOS研究方向	Pharmacology & Pharmacy (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:4195754
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/267888]
专题	中国科学院上海药物研究所
作者单位	1.Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.; 2.Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai 201203, China.
推荐引用方式 GB/T 7714	GU Shunlin,MA Zhilong,LI Yali,et al. Design,synthesis and anti-schizophrenia activity of 3,4-dihydroquinolin-2(1H)-one derivatives[J]. Chinese Journal of Medicinal Chemistry,2011,21(2):81-87.
APA	GU Shunlin,MA Zhilong,LI Yali,YU Leiping,&LI Jianqi.(2011).Design,synthesis and anti-schizophrenia activity of 3,4-dihydroquinolin-2(1H)-one derivatives.Chinese Journal of Medicinal Chemistry,21(2),81-87.
MLA	GU Shunlin,et al."Design,synthesis and anti-schizophrenia activity of 3,4-dihydroquinolin-2(1H)-one derivatives".Chinese Journal of Medicinal Chemistry 21.2(2011):81-87.