New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity γ-Hydroxybutyrate (GHB) Binding Sites
| Autor: | Christoffer Bundgaard, Aleš Marek, Jan Kehler, Stine B. Vogensen, Martin Holst Friborg Pedersen, Rasmus P. Clausen, Bente Frølund, Petrine Wellendorph, Tina Bay |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Central Nervous System
Male Stereochemistry Carboxylic Acids Synaptic Membranes Hydroxybutyrates Cyclopentanes Ligands Tritium Binding Competitive Article Cell Line Rats Sprague-Dawley Radioligand Assay Drug Stability In vivo Drug Discovery Animals Binding site gamma-Aminobutyric Acid Binding Sites Molecular Structure Chemistry Ligand Radiosynthesis Brain In vitro Rats Benzocycloheptenes Kinetics Models Chemical Molecular Medicine Selectivity |
| Popis: | 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 [(3)H]-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 [(3)H]-1 binding shows high specificity to the high-affinity GHB binding sites. |
| Databáze: | OpenAIRE |
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