New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-Affinity 纬-Hydroxybutyrate (GHB) Binding Sites
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- 作者：Stine B. Vogensen ; Ale拧 Marek ; Tina Bay ; Petrine Wellendorph ; Jan Kehler ; Christoffer Bundgaard ; Bente Fr酶lund ; Martin H. F. Pedersen ; Rasmus P. Clausen
- 刊名：Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：October 24, 2013
- 年：2013
- 卷：56
- 期：20
- 页码：8201-8205
- 全文大小：249K
- 年卷期：v.56,no.20(October 24, 2013)
- ISSN：1520-4804
文摘
3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, <b>1b>) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of <b>1b> together with a very efficient synthesis of [3H]-<b>1b> is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of <b>1b> against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain penetration. In vitro characterization of [3H]-<b>1b> binding shows high specificity to the high-affinity GHB binding sites.