Advanced

Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABAA receptors.

Lager, Erik LU ; Nilsson, Jakob LU ; Østergaard Nielsen, Elsebet; Nielsen, Mogens; Liljefors, Tommy and Sterner, Olov LU (2008) In Bioorganic & Medicinal Chemistry 16(14). p.6936-6948
Abstract
The finding that alkyl 1,4-dihydro-4-oxoquinoline-3-carboxylate and N-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxamide derivatives may be high-affinity ligands at the benzodiazepine binding site of the GABAA receptor, prompted a study of 3-acyl-1,4-dihydro-4-oxoquinoline (3-acyl-4-quinolones). In general, the affinity of the 3-acyl derivatives was found to be comparable with the 3-carboxylate and the 3-carboxamide derivatives, and certain substituents (e.g., benzyl) in position 6 were again shown to be important. As it is believed that the benzodiazepine binding site is situated between an α- and a γ-subunit in the GABAA receptor, selected compounds were tested on the α1β2γ2s, α2β2γ2s and α3β2γ2s GABAA receptor subtypes. The... (More)
The finding that alkyl 1,4-dihydro-4-oxoquinoline-3-carboxylate and N-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxamide derivatives may be high-affinity ligands at the benzodiazepine binding site of the GABAA receptor, prompted a study of 3-acyl-1,4-dihydro-4-oxoquinoline (3-acyl-4-quinolones). In general, the affinity of the 3-acyl derivatives was found to be comparable with the 3-carboxylate and the 3-carboxamide derivatives, and certain substituents (e.g., benzyl) in position 6 were again shown to be important. As it is believed that the benzodiazepine binding site is situated between an α- and a γ-subunit in the GABAA receptor, selected compounds were tested on the α1β2γ2s, α2β2γ2s and α3β2γ2s GABAA receptor subtypes. The 3-acyl-4-quinolones display various degrees of selectivity for α1- versus α2- and α3-containing receptors, and high-affinity ligands essentially selective for α1 over α3 were developed. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
3-Acyl-1, 4-dihydro-4-oxoquinolines, Benzodiazepine binding site, GABAA receptor, GABAA receptor subtypes, Pharmacophore model
in
Bioorganic & Medicinal Chemistry
volume
16
issue
14
pages
6936 - 6948
publisher
Elsevier
external identifiers
  • wos:000257829600032
  • scopus:47349094959
ISSN
0968-0896
DOI
10.1016/j.bmc.2008.05.049
language
English
LU publication?
yes
id
17947d01-3080-411d-be57-61abe6ff18ec (old id 1214985)
date added to LUP
2008-08-14 15:49:49
date last changed
2017-01-01 04:41:24
@article{17947d01-3080-411d-be57-61abe6ff18ec,
  abstract     = {The finding that alkyl 1,4-dihydro-4-oxoquinoline-3-carboxylate and N-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxamide derivatives may be high-affinity ligands at the benzodiazepine binding site of the GABAA receptor, prompted a study of 3-acyl-1,4-dihydro-4-oxoquinoline (3-acyl-4-quinolones). In general, the affinity of the 3-acyl derivatives was found to be comparable with the 3-carboxylate and the 3-carboxamide derivatives, and certain substituents (e.g., benzyl) in position 6 were again shown to be important. As it is believed that the benzodiazepine binding site is situated between an α- and a γ-subunit in the GABAA receptor, selected compounds were tested on the α1β2γ2s, α2β2γ2s and α3β2γ2s GABAA receptor subtypes. The 3-acyl-4-quinolones display various degrees of selectivity for α1- versus α2- and α3-containing receptors, and high-affinity ligands essentially selective for α1 over α3 were developed.},
  author       = {Lager, Erik and Nilsson, Jakob and Østergaard Nielsen, Elsebet and Nielsen, Mogens and Liljefors, Tommy and Sterner, Olov},
  issn         = {0968-0896},
  keyword      = {3-Acyl-1,4-dihydro-4-oxoquinolines,Benzodiazepine binding site,GABAA receptor,GABAA receptor subtypes,Pharmacophore model},
  language     = {eng},
  number       = {14},
  pages        = {6936--6948},
  publisher    = {Elsevier},
  series       = {Bioorganic & Medicinal Chemistry},
  title        = {Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABAA receptors.},
  url          = {http://dx.doi.org/10.1016/j.bmc.2008.05.049},
  volume       = {16},
  year         = {2008},
}