Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands : design, synthesis, and binding studies. / Høg, Signe; Wellendorph, Petrine; Nielsen, Birgitte; Frydenvang, Karla; Dahl, Ivar F; Bräuner-Osborne, Hans; Brehm, Lotte; Frølund, Bente; Clausen, Rasmus P.

In: Journal of Medicinal Chemistry, Vol. 51, No. 24, 2008, p. 8088-8095.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Høg, S, Wellendorph, P, Nielsen, B, Frydenvang, K, Dahl, IF, Bräuner-Osborne, H, Brehm, L, Frølund, B & Clausen, RP 2008, 'Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies', Journal of Medicinal Chemistry, vol. 51, no. 24, pp. 8088-8095. https://doi.org/10.1021/jm801112u

APA

Høg, S., Wellendorph, P., Nielsen, B., Frydenvang, K., Dahl, I. F., Bräuner-Osborne, H., ... Clausen, R. P. (2008). Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies. Journal of Medicinal Chemistry, 51(24), 8088-8095. https://doi.org/10.1021/jm801112u

Vancouver

Høg S, Wellendorph P, Nielsen B, Frydenvang K, Dahl IF, Bräuner-Osborne H et al. Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies. Journal of Medicinal Chemistry. 2008;51(24):8088-8095. https://doi.org/10.1021/jm801112u

Author

Høg, Signe ; Wellendorph, Petrine ; Nielsen, Birgitte ; Frydenvang, Karla ; Dahl, Ivar F ; Bräuner-Osborne, Hans ; Brehm, Lotte ; Frølund, Bente ; Clausen, Rasmus P. / Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands : design, synthesis, and binding studies. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 24. pp. 8088-8095.

Bibtex

@article{7b93d640e3a811ddbf70000ea68e967b,
title = "Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies",
abstract = "Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites in brain, of which the latter have not been linked unequivocally to function, but are speculated to be GHB receptors. In this study, a series of biaromatic 4-substituted GHB analogues, including 4'-phenethylphenyl, 4'-styrylphenyl, and 4'-benzyloxyphenyl GHB analogues, were synthesized and characterized pharmacologically in a [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([3H]NCS-382) binding assay and in GABA(A) and GABA(B) receptor binding assays. The compounds were selective for the high-affinity GHB binding sites and several displayed Ki values below 100 nM. The affinity of the 4-[4'-(2-iodobenzyloxy)phenyl] GHB analogue 17b was shown to reside predominantly with the R-enantiomer (Ki = 22 nM), which has higher affinity than previously reported GHB ligands.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Signe H{\o}g and Petrine Wellendorph and Birgitte Nielsen and Karla Frydenvang and Dahl, {Ivar F} and Hans Br{\"a}uner-Osborne and Lotte Brehm and Bente Fr{\o}lund and Clausen, {Rasmus P}",
year = "2008",
doi = "10.1021/jm801112u",
language = "English",
volume = "51",
pages = "8088--8095",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "24",

}

RIS

TY - JOUR

T1 - Novel high-affinity and selective biaromatic 4-substituted ¿-hydroxybutyric acid (GHB) analogues as GHB ligands

T2 - design, synthesis, and binding studies

AU - Høg, Signe

AU - Wellendorph, Petrine

AU - Nielsen, Birgitte

AU - Frydenvang, Karla

AU - Dahl, Ivar F

AU - Bräuner-Osborne, Hans

AU - Brehm, Lotte

AU - Frølund, Bente

AU - Clausen, Rasmus P

PY - 2008

Y1 - 2008

N2 - Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites in brain, of which the latter have not been linked unequivocally to function, but are speculated to be GHB receptors. In this study, a series of biaromatic 4-substituted GHB analogues, including 4'-phenethylphenyl, 4'-styrylphenyl, and 4'-benzyloxyphenyl GHB analogues, were synthesized and characterized pharmacologically in a [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([3H]NCS-382) binding assay and in GABA(A) and GABA(B) receptor binding assays. The compounds were selective for the high-affinity GHB binding sites and several displayed Ki values below 100 nM. The affinity of the 4-[4'-(2-iodobenzyloxy)phenyl] GHB analogue 17b was shown to reside predominantly with the R-enantiomer (Ki = 22 nM), which has higher affinity than previously reported GHB ligands.

AB - Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites in brain, of which the latter have not been linked unequivocally to function, but are speculated to be GHB receptors. In this study, a series of biaromatic 4-substituted GHB analogues, including 4'-phenethylphenyl, 4'-styrylphenyl, and 4'-benzyloxyphenyl GHB analogues, were synthesized and characterized pharmacologically in a [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([3H]NCS-382) binding assay and in GABA(A) and GABA(B) receptor binding assays. The compounds were selective for the high-affinity GHB binding sites and several displayed Ki values below 100 nM. The affinity of the 4-[4'-(2-iodobenzyloxy)phenyl] GHB analogue 17b was shown to reside predominantly with the R-enantiomer (Ki = 22 nM), which has higher affinity than previously reported GHB ligands.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jm801112u

DO - 10.1021/jm801112u

M3 - Journal article

C2 - 19053823

VL - 51

SP - 8088

EP - 8095

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 24

ER -

ID: 9768917