Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors

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

Standard

Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors. / Nilsson, Jakob; Gidlöf, Ritha; Nielsen, Elsebet Østergaard; Liljefors, Tommy; Nielsen, Mogens Peter Cherly; Sterner, Olov.

In: Bioorganic & Medicinal Chemistry, Vol. 19, No. 1, 01.01.2011, p. 111-121.

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

Harvard

Nilsson, J, Gidlöf, R, Nielsen, EØ, Liljefors, T, Nielsen, MPC & Sterner, O 2011, 'Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors', Bioorganic & Medicinal Chemistry, vol. 19, no. 1, pp. 111-121. https://doi.org/10.1016/j.bmc.2010.11.050

APA

Nilsson, J., Gidlöf, R., Nielsen, E. Ø., Liljefors, T., Nielsen, M. P. C., & Sterner, O. (2011). Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors. Bioorganic & Medicinal Chemistry, 19(1), 111-121. https://doi.org/10.1016/j.bmc.2010.11.050

Vancouver

Nilsson J, Gidlöf R, Nielsen EØ, Liljefors T, Nielsen MPC, Sterner O. Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors. Bioorganic & Medicinal Chemistry. 2011 Jan 1;19(1):111-121. https://doi.org/10.1016/j.bmc.2010.11.050

Author

Nilsson, Jakob ; Gidlöf, Ritha ; Nielsen, Elsebet Østergaard ; Liljefors, Tommy ; Nielsen, Mogens Peter Cherly ; Sterner, Olov. / Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors. In: Bioorganic & Medicinal Chemistry. 2011 ; Vol. 19, No. 1. pp. 111-121.

Bibtex

@article{fe2f9ec3d7bc4c5d8a980992c6af61e5,
title = "Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors",
abstract = "Based on a pharmacophore model of the benzodiazepine-binding site of GABA(A) receptors, a series of 2-aryl-2,6-dihydro[1,2,4]triazolo[4,3-c]quinazoline-3,5-diones (structure type I) were designed, synthesized, and identified as high-affinity ligands of the binding site. For several compounds, K(i) values of around 0.20nM were determined. They show a structural resemblance with the previously described 2-phenyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones (II) and 2-phenyl-[1,2,4]triazolo[1,5-a]quinoxalin-4(5H)-one (III). The 9-bromo substituted compounds 8a-d were prepared in an 8-step synthesis in an overall yield of approximately 40%, and a library of 9-substituted analogues was prepared by cross-coupling reactions. Compound 8e, 21, 22, and 24 were tested on recombinant rat a(1){\ss}(3)¿(2), a(2){\ss}(3)¿(2), a(3){\ss}(3)¿(2), and a(5){\ss}(3)¿(2) subtypes, and displayed selectivity for the a(1){\ss}(3)¿(2) isoform.",
keywords = "Animals, Benzodiazepines, Ligands, Magnetic Resonance Spectroscopy, Models, Molecular, Protein Binding, Quinazolines, Rats, Receptors, GABA-A, Spectrometry, Mass, Electrospray Ionization, Former Faculty of Pharmaceutical Sciences",
author = "Jakob Nilsson and Ritha Gidl{\"o}f and Nielsen, {Elsebet {\O}stergaard} and Tommy Liljefors and Nielsen, {Mogens Peter Cherly} and Olov Sterner",
note = "Keywords: 2-aryl-2,6-dihydro[1,2,4]triazolo-[4,3-c]quinazoline-3,5-diones; benzodiazepine binding site; GABA(A) receptors; GABA(A) receptor subtypes; pharmacophore model",
year = "2011",
month = jan,
day = "1",
doi = "10.1016/j.bmc.2010.11.050",
language = "English",
volume = "19",
pages = "111--121",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",
publisher = "Pergamon Press",
number = "1",

}

RIS

TY - JOUR

T1 - Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors

AU - Nilsson, Jakob

AU - Gidlöf, Ritha

AU - Nielsen, Elsebet Østergaard

AU - Liljefors, Tommy

AU - Nielsen, Mogens Peter Cherly

AU - Sterner, Olov

N1 - Keywords: 2-aryl-2,6-dihydro[1,2,4]triazolo-[4,3-c]quinazoline-3,5-diones; benzodiazepine binding site; GABA(A) receptors; GABA(A) receptor subtypes; pharmacophore model

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Based on a pharmacophore model of the benzodiazepine-binding site of GABA(A) receptors, a series of 2-aryl-2,6-dihydro[1,2,4]triazolo[4,3-c]quinazoline-3,5-diones (structure type I) were designed, synthesized, and identified as high-affinity ligands of the binding site. For several compounds, K(i) values of around 0.20nM were determined. They show a structural resemblance with the previously described 2-phenyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones (II) and 2-phenyl-[1,2,4]triazolo[1,5-a]quinoxalin-4(5H)-one (III). The 9-bromo substituted compounds 8a-d were prepared in an 8-step synthesis in an overall yield of approximately 40%, and a library of 9-substituted analogues was prepared by cross-coupling reactions. Compound 8e, 21, 22, and 24 were tested on recombinant rat a(1)ß(3)¿(2), a(2)ß(3)¿(2), a(3)ß(3)¿(2), and a(5)ß(3)¿(2) subtypes, and displayed selectivity for the a(1)ß(3)¿(2) isoform.

AB - Based on a pharmacophore model of the benzodiazepine-binding site of GABA(A) receptors, a series of 2-aryl-2,6-dihydro[1,2,4]triazolo[4,3-c]quinazoline-3,5-diones (structure type I) were designed, synthesized, and identified as high-affinity ligands of the binding site. For several compounds, K(i) values of around 0.20nM were determined. They show a structural resemblance with the previously described 2-phenyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones (II) and 2-phenyl-[1,2,4]triazolo[1,5-a]quinoxalin-4(5H)-one (III). The 9-bromo substituted compounds 8a-d were prepared in an 8-step synthesis in an overall yield of approximately 40%, and a library of 9-substituted analogues was prepared by cross-coupling reactions. Compound 8e, 21, 22, and 24 were tested on recombinant rat a(1)ß(3)¿(2), a(2)ß(3)¿(2), a(3)ß(3)¿(2), and a(5)ß(3)¿(2) subtypes, and displayed selectivity for the a(1)ß(3)¿(2) isoform.

KW - Animals

KW - Benzodiazepines

KW - Ligands

KW - Magnetic Resonance Spectroscopy

KW - Models, Molecular

KW - Protein Binding

KW - Quinazolines

KW - Rats

KW - Receptors, GABA-A

KW - Spectrometry, Mass, Electrospray Ionization

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.bmc.2010.11.050

DO - 10.1016/j.bmc.2010.11.050

M3 - Journal article

C2 - 21163663

VL - 19

SP - 111

EP - 121

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 1

ER -

ID: 35378899