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

Stine B. Vogensen; Ales Marek; Tina Bay; Petrine Wellendorph; Jan Kehler; Christoffer Bundgaard; Bente Frølund; Martin Holst Friborg Pedersen; Rasmus P. Clausen

doi:10.1021/jm4011719

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

Stine B. Vogensen, Ales Marek, Tina Bay, Petrine Wellendorph, Jan Kehler, Christoffer Bundgaard, Bente Frølund, Martin Holst Friborg Pedersen, Rasmus P. Clausen

Research output: Contribution to journal › Journal article › Research › peer-review

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 [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.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	56
Issue number	20
Pages (from-to)	8201-8205
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm4011719
Publication status	Published - 2013

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title = "New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-Affinity γ-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 [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.",

author = "Vogensen, {Stine B.} and Ales Marek and Tina Bay and Petrine Wellendorph and Jan Kehler and Christoffer Bundgaard and Bente Fr{\o}lund and Pedersen, {Martin Holst Friborg} and Clausen, {Rasmus P.}",

year = "2013",

doi = "10.1021/jm4011719",

language = "English",

volume = "56",

pages = "8201--8205",

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TY - JOUR

T1 - New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-Affinity γ-Hydroxybutyrate (GHB) Binding Sites

AU - Vogensen, Stine B.

AU - Marek, Ales

AU - Bay, Tina

AU - Wellendorph, Petrine

AU - Kehler, Jan

AU - Bundgaard, Christoffer

AU - Frølund, Bente

AU - Pedersen, Martin Holst Friborg

AU - Clausen, Rasmus P.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1021/jm4011719

DO - 10.1021/jm4011719

M3 - Journal article

C2 - 24053696

SN - 0022-2623

VL - 56

SP - 8201

EP - 8205

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 20

ER -

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

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