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'Click' D-1 receptor agonists with a 5-HT1A receptor pharmacophore producing D-2 receptor activity

文献类型：期刊论文

作者Zhang, Jing1; Zhang, Hai2; Cai, Wenxian2; Yu, Leiping2; Zhen, Xuechu2; Zhang, Ao1
刊名BIOORGANIC & MEDICINAL CHEMISTRY
出版日期2009-07-15
卷号17期号:14页码:4873-4880
ISSN号0968-0896
关键词Arylbenzazepine Arylpiperazine Click reaction Dopamine receptor Serotonin 5-HT1A receptor
DOI10.1016/j.bmc.2009.06.019
文献子类Article
英文摘要A series of new 1-aryl-3-benzazepine derivatives containing an arylpiperazinyl function as the N3 substituent were synthesized by combining a D-1 receptor agonistic pharmacophore and a 5-HT1A receptor pharmacophore through Click reaction. Interestingly, these compounds generally do not have good binding affinity at the D-1 receptor, but most compounds are potent at both D-2 and 5-HT1A receptors. Compound 8h, containing 1-m-tolyl-benzazepine scaffold and 2-methoxyphenylpiperazine core, displayed good affinity at all tested receptors, with K-i values of 144, 80, and 133 nM, for the D-1, D-2, and 5-HT1A receptors, respectively. Compound 13 with the triazole moiety formed differently from that in 8h showed the highest affinity at the D-2 receptor with K-i value of 19 nM. This compound also showed moderate affinity at the 5-HT1A (K-i, 105 nM), and D-1 (K-i, 551 nM) receptors. Functional assays indicated that both compounds 13 and 8h are antagonists at D-1 and D-2 receptors, whereas full agonistic activity at the 5-HT1A receptor was observed. In agreement with the binding affinity, compound 13 is a high efficacy D-2 antagonist and 5-HT1A agonist. (C) 2009 Elsevier Ltd. All rights reserved.
WOS关键词PARKINSONS-DISEASE ; SEROTONIN ; LIGANDS ; COMPLICATIONS ; DOPAMINE-D-2 ; THERAPEUTICS ; DERIVATIVES ; THERAPY
资助项目Chinese National Science Foundation[30772625] ; Chinese National Science Foundation[30672517] ; Shanghai Commission of Science and Technology[07pj14104] ; Ministry of Science and Technology[2007AA022163] ; Chinese Academy of Sciences[00000000] ; Shanghai Institute of Materia Medica[00000000]
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种英语
出版者PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号WOS:000267873000003
源URL[http://119.78.100.183/handle/2S10ELR8/279183]  
专题药物化学研究室
药理学第二研究室
通讯作者Zhen, Xuechu
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, 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		 Zhang, Jing,Zhang, Hai,Cai, Wenxian,et al. 'Click' D-1 receptor agonists with a 5-HT1A receptor pharmacophore producing D-2 receptor activity[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2009,17(14):4873-4880.
APA Zhang, Jing,Zhang, Hai,Cai, Wenxian,Yu, Leiping,Zhen, Xuechu,&Zhang, Ao.(2009).'Click' D-1 receptor agonists with a 5-HT1A receptor pharmacophore producing D-2 receptor activity.BIOORGANIC & MEDICINAL CHEMISTRY,17(14),4873-4880.
MLA Zhang, Jing,et al."'Click' D-1 receptor agonists with a 5-HT1A receptor pharmacophore producing D-2 receptor activity".BIOORGANIC & MEDICINAL CHEMISTRY 17.14(2009):4873-4880.

入库方式： OAI收割

来源：上海药物研究所

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