Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors.
(2011) In Bioorganic & Medicinal Chemistry 19(1). p.111-121- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1756250
- author
- Nilsson, Jakob LU ; Gidlöf, Ritha LU ; Nielsen, Elsebet Østergaard ; Liljefors, Tommy ; Nielsen, Mogens and Sterner, Olov LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Bioorganic & Medicinal Chemistry
- volume
- 19
- issue
- 1
- pages
- 111 - 121
- publisher
- Elsevier
- external identifiers
-
- wos:000285724800011
- pmid:21163663
- scopus:78650744695
- ISSN
- 0968-0896
- DOI
- 10.1016/j.bmc.2010.11.050
- language
- English
- LU publication?
- yes
- additional info
- 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)
- id
- c5c4c6fe-0bfd-48f0-bd8c-40addf361273 (old id 1756250)
- date added to LUP
- 2016-04-01 10:48:06
- date last changed
- 2022-01-26 02:38:09
@article{c5c4c6fe-0bfd-48f0-bd8c-40addf361273,
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 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.}},
author = {{Nilsson, Jakob and Gidlöf, Ritha and Nielsen, Elsebet Østergaard and Liljefors, Tommy and Nielsen, Mogens and Sterner, Olov}},
issn = {{0968-0896}},
language = {{eng}},
number = {{1}},
pages = {{111--121}},
publisher = {{Elsevier}},
series = {{Bioorganic & Medicinal Chemistry}},
title = {{Triazoloquinazolinediones as novel high affinity ligands for the benzodiazepine site of GABA(A) receptors.}},
url = {{http://dx.doi.org/10.1016/j.bmc.2010.11.050}},
doi = {{10.1016/j.bmc.2010.11.050}},
volume = {{19}},
year = {{2011}},
}