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

TY - JOUR

T1 - New synthesis and tritium labeling of a selective ligand for studying high-affinity γ-hydroxybutyrate (GHB) binding sites

AU - Vogensen, Stine Byskov

AU - Marek, A

AU - Bay, Tina

AU - Wellendorph, Petrine

AU - Kehler, J

AU - Bundgaard, C

AU - Frølund, Bente

AU - Pedersen, M.H.F.

AU - Clausen, Rasmus Prætorius

PY - 2013/10/24

Y1 - 2013/10/24

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 -