Synthesis of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)1H-pyrrole analogues and their binding affinities for dopamine D2, D3, and D4 receptors
Synthesis of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)1H-pyrrole analogues and their binding affinities for dopamine D2, D3, and D4 receptors
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DOI：
10.1016/s0968-0896(02)00341-3
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发表时间：
2003-01-17
影响因子：
3.5
通讯作者：
Luedtke, RR
中科院分区：
文献类型：
--
作者：
Mach, RH;Huang, YS;Luedtke, RR
制备了一系列2-（5-溴-2，3-二甲氧基苯基）-5-（氨甲基）-1H-吡咯类似物，并使用体外结合试验测量了它们对多巴胺D-2、D-3和D-4受体的亲和力。受体结合研究的结果表明，在苯环和碱性氮之间掺入吡咯部分导致多巴胺D-3受体的选择性显着增加。该系列中最具选择性的化合物是2-（5-溴-2，3-二甲氧基苯基）-5-（2-（3-吡啶）哌啶基）甲基-1H-吡咯（6p），其D-3受体亲和力为4.3 nM，对D-3受体的选择性是对D-2受体的20倍，对D-3受体的选择性是对D-4受体的300倍。该化合物被预测为用于研究体内多巴胺D-3受体的功能作用的有用配体。(C)2002爱思唯尔科技有限公司版权所有。
A series of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues was prepared and their affinity for dopamine D-2, D-3, and D-4 receptors was measured using in vitro binding assays. The results of receptor binding studies indicated that the incorporation of a pyrrole moiety between the phenyl ring and the basic nitrogen resulted in a significant increase in the selectivity for dopamine D-3 receptors. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-5-(2-(3-pyridal)piperidinyl)methyl-1H-pyrrole (6p), which has a D-3 receptor affinity of 4.3 nM, a 20-fold selectivity for D-3 versus D-2 receptors, and a 300-fold selectivity for D-3 versus D-4 receptors. This compound is predicted to be a useful ligand for studying the functional role of dopamine D-3 receptors in vivo. (C) 2002 Elsevier Science Ltd. All rights reserved.