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New synthesis and tritium labeling of a selective ligand for studying high-affinity ?-hydroxybutyrate (GHB) binding sites.

ABSTRACT: 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.

SUBMITTER: Vogensen SB

PROVIDER: S-EPMC3888956 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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New synthesis and tritium labeling of a selective ligand for studying high-affinity γ-hydroxybutyrate (GHB) binding sites.

Vogensen Stine B SB Marek Aleš A Bay Tina T Wellendorph Petrine P Kehler Jan J Bundgaard Christoffer C Frølund Bente B Pedersen Martin H F MH Clausen Rasmus P RP

Journal of medicinal chemistry 20131004 20

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-aff ...[more]

PMID: 24053696

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