Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist

doi:10.1021/jm9015763

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist
	Liu, Zhili 1; Zhang, Hai 2; Ye, Na 1; Zhang, Jing 1; Wu, QianQian 2; Sun, Peihua 2; Li, Linyong 2; Zhen, Xuechu 2; Zhang, Ao1
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2010-02-11
卷号	53 期号:3 页码:1319-1328
ISSN号	0022-2623
DOI	10.1021/jm9015763
文献子类	Article
英文摘要	A series of new aporphine analogues were synthesized and pharmacologically evaluated. 11-Allyloxy-(17), 11-propargyloxy-(20), and dihydrofuro-(19) aporphines displayed the highest affinity at the 5-HT1A receptor with K-i values of 12.0, 14.0, and 6.7 nM, respectively. The high binding potential of the diastereomeric mixture of aporphine 19 was found residing in the cis-diastereomer (cis-19). [S-35]GTP gamma S function assays on 5-HT1A receptor indicated that aporphines 17 and 20 were partial agonists, while trans-19 behaved as a high efficacy full antagonist and cis-19 was a full agonist. The agonistic property of cis-19 at the 5-HT1A receptor was further confirmed in vitro and in vivo. This compound may be useful as a potential treatment for anxiety.
资助项目	Chinese National Science Foundation[30772625] ; Chinese National Science Foundation[30672517] ; National Science Technology[2009ZX09103-062] ; National Science Technology[2009ZX09301-001] ; [2007AA022163]
WOS关键词	VENTRAL TEGMENTAL AREA ; NIGRAL DOPAMINE NEURONS ; ELEVATED PLUS-MAZE ; (R)-APORPHINES SYNTHESIS ; PARKINSONS-DISEASE ; RAPHE NUCLEUS ; RAT ; PHARMACOLOGY ; ANXIETY ; COMPLICATIONS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000274270900036
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278972]
专题	药理学第二研究室药物化学研究室
通讯作者	Zhen, Xuechu
作者单位	1.Chinese Acad Sci, SOMCL, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Neuropharmacol Lab, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Liu, Zhili,Zhang, Hai,Ye, Na,et al. Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist[J]. JOURNAL OF MEDICINAL CHEMISTRY,2010,53(3):1319-1328.
APA	Liu, Zhili.,Zhang, Hai.,Ye, Na.,Zhang, Jing.,Wu, QianQian.,...&Zhang, Ao.(2010).Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist.JOURNAL OF MEDICINAL CHEMISTRY,53(3),1319-1328.
MLA	Liu, Zhili,et al."Synthesis of Dihydrofuroaporphine Derivatives: Identification of a Potent and Selective Serotonin 5-HT1A Receptor Agonist".JOURNAL OF MEDICINAL CHEMISTRY 53.3(2010):1319-1328.