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

Research output: Contribution to journalArticle

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; Sterner, Olov.

In: Bioorganic & Medicinal Chemistry, Vol. 19, No. 1, 2011, p. 111-121.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

Nilsson, Jakob ; Gidlöf, Ritha ; Nielsen, Elsebet Østergaard ; Liljefors, Tommy ; Nielsen, Mogens ; 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.

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

AU - Sterner, Olov

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)

PY - 2011

Y1 - 2011

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 α(1)β(3)γ(2), α(2)β(3)γ(2), α(3)β(3)γ(2), and α(5)β(3)γ(2) subtypes, and displayed selectivity for the α(1)β(3)γ(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 α(1)β(3)γ(2), α(2)β(3)γ(2), α(3)β(3)γ(2), and α(5)β(3)γ(2) subtypes, and displayed selectivity for the α(1)β(3)γ(2) isoform.

U2 - 10.1016/j.bmc.2010.11.050

DO - 10.1016/j.bmc.2010.11.050

M3 - Article

VL - 19

SP - 111

EP - 121

JO - Bioorganic and Medicinal Chemistry

T2 - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 1

ER -