一种基于吡咯戊酮的新型多巴胺转运体光亲和配体。
A novel photoaffinity ligand for the dopamine transporter based on pyrovalerone.
作者信息
Lapinsky David J, Aggarwal Shaili, Huang Yurong, Surratt Christopher K, Lever John R, Foster James D, Vaughan Roxanne A
机构信息
Division of Pharmaceutical Sciences, Duquesne University Mylan School of Pharmacy, 600 Forbes Avenue, Pittsburgh, PA 15282, USA.
出版信息
Bioorg Med Chem. 2009 Jun 1;17(11):3770-4. doi: 10.1016/j.bmc.2009.04.057. Epub 2009 May 3.
Abstract
Non-tropane-based photoaffinity ligands for the dopamine transporter (DAT) are relatively unexplored in contrast to tropane-based compounds such as cocaine. In order to fill this knowledge gap, a ligand was synthesized in which the aromatic ring of pyrovalerone was substituted with a photoreactive azido group. The analog 1-(4-azido-3-iodophenyl)-2-pyrrolidin-1-yl-pentan-1-one demonstrated appreciable binding affinity for the DAT (K(i)=78+/-18 nM), suggesting the potential utility of a radioiodinated version in structure-function studies of this protein.
摘要
与可卡因等基于托烷的化合物相比，用于多巴胺转运体（DAT）的非托烷类光亲和配体相对较少被研究。为了填补这一知识空白，合成了一种配体，其中吡咯戊酮的芳香环被光反应性叠氮基取代。类似物1-(4-叠氮基-3-碘苯基)-2-吡咯烷-1-基-戊-1-酮对DAT表现出可观的结合亲和力（K(i)=78±18 nM），这表明放射性碘化版本在该蛋白质的结构-功能研究中具有潜在用途。
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Ann Clin Psychiatry. 2008 Jul-Sep;20(3):145-55. doi: 10.1080/10401230802177656.
3
The search for medications to treat stimulant dependence.
Addict Sci Clin Pract. 2008 Jun;4(2):28-35. doi: 10.1151/ascp084228.
4
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