New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity γ-Hydroxybutyrate (GHB) Binding Sites

摘要

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.