Further exploration of 1-[2-[Bis-(4-fluorophenyl)methoxy]ethyl]piperazine (GBR 12909): role of N-aromatic, N-heteroaromatic, and 3-oxygenated N-phenylpropyl substituents on affinity for the dopamine and serotonin transporter.
Further exploration of 1-[2-[Bis-(4-fluorophenyl)methoxy]ethyl]piperazine (GBR 12909): role of N-aromatic, N-heteroaromatic, and 3-oxygenated N-phenylpropyl substituents on affinity for the dopamine and serotonin transporter.
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1-[2-[双-(4-氟苯基)甲氧基]乙基]哌嗪 (GBR 12909) 的进一步探索：N-芳香族、N-杂芳香族和 3-氧化 N-苯基丙基取代基对多巴胺和亲和力的作用
DOI：
10.1016/s0960-894x(03)00108-2
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发表时间：
2003
影响因子：
2.7
通讯作者：
Rice,KennerC
中科院分区：
文献类型：
--
作者：
Lewis,David;Zhang,Ying;Prisinzano,Thomas;Dersch,ChristinaM;Rothman,RichardB;Jacobson,ArthurE;Rice,KennerC
合成了1-（2-苯并羟基氧乙基）-哌嗪和1-{2-[双-（4-氟苯基）甲氧基]乙基}哌嗪的n -芳香、n -杂芳香和氧合的n -苯丙基衍生物，它们是GBR 12909 （1a）和12935 （1b）的类似物，并研究了它们与多巴胺（DAT）和血清素（SERT）转运体的结合特性。其中一种外消旋化合物3-[4-（2-苯并羟基氧乙基）哌嗪-1-基]-1-（3-氟苯基）-丙-1-醇（33）具有与GBR 12909和12935相同或更好的DAT亲和力，并且在SERT上对DAT的选择性比GBR化合物更强。反式-(43)和顺式-(47)（±）-2-（4-{2-[双-（4-氟苯基）-甲氧基]乙基}哌嗪-1-甲基）-6-甲氧基-1,2,3,4-四氢萘-1-醇均具有较好的SERT选择性，且对SERT具有较高的亲和力。
A series of N-aromatic, N-heteroaromatic, and oxygenated N-phenylpropyl derivatives of 1-(2-benzhydryloxyethyl)-piperazine and 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}piperazine, analogues of GBR 12909 (1a) and 12935 (1b), was synthesized and examined for their dopamine (DAT) and serotonin (SERT) transporter binding properties. One of these compounds, racemic 3-[4-(2-benzhydryloxyethyl)piperazin-1-yl]-1-(3-fluorophenyl)-propan-1-ol (33), had DAT affinity as good as, or better than, GBR 12909 and 12935, and was more selective for DAT over SERT than the GBR compounds. Both trans- (43) and cis- (47) (±)-2-(4-{2-[bis-(4-fluorophenyl)-methoxy]ethyl}piperazin-1-ylmethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol had relatively good SERT selectivity and, as well, showed high affinity for SERT.