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, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [³H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain penetration. In vitro characterization of [³H]-1 binding shows high specificity to the high-affinity GHB binding sites.