N-hydroxyalkyl derivatives of 3 beta-phenyltropane and 1-methylspiro[1H-indoline-3,4'-piperidine]: Vesamicol analogues with affinity for monoamine transporters
N-hydroxyalkyl derivatives of 3 beta-phenyltropane and 1-methylspiro[1H-indoline-3,4'-piperidine]: Vesamicol analogues with affinity for monoamine transporters
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DOI：
10.1021/jm970326r
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发表时间：
1997-11-21
影响因子：
7.3
通讯作者：
Parsons, SM
中科院分区：
文献类型：
--
作者：
Efange, SMN;Kamath, AP;Parsons, SM
作为我们正在进行的囊泡乙酰胆碱转运蛋白配体2-（4-苯基哌啶子基）环己醇（维索霉素，1）的结构-活性研究的一部分，合成了3 β-苯基托烷的22个N-羟基（苯基）烷基衍生物，6和1-甲基螺[1H-二氢吲哚-3，4 '-哌啶]，7，并进行了体外结合测试。虽然一些化合物显示出适度高的亲和力的囊泡乙酰胆碱转运蛋白，没有化合物是更有效的比原型囊泡乙酰胆碱转运蛋白配体vesamicol。然而，6的一些衍生物显示出比可卡因更高的多巴胺转运蛋白的亲和力。我们的结论是，1的哌啶基片段的修改将不会导致更有效的囊泡乙酰胆碱转运蛋白配体。
As part of our ongoing structure-activity studies of the vesicular acetylcholine transporter ligand 2-(4-phenylpiperidino)cyclohexanol (vesamicol, 1), 22 N-hydroxy(phenyl)alkyl derivatives of 3 beta-phenyltropane, 6, and 1-methylspiro[1H-indoline-3,4'-piperidine], 7, were synthesized and tested for binding in vitro. Although a few compounds displayed moderately high affinity for the vesicular acetylcholine transporter, no compound was more potent than the prototypical vesicular acetylcholine transporter ligand vesamicol. However, a few derivatives of 6 displayed higher affinity for the dopamine transporter than cocaine. We conclude that modification of the piperidyl fragment of 1 will not lead to more potent vesicular acetylcholine transporter ligands.