Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABAA receptors.
(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:
https://lup.lub.lu.se/record/1214985
- author
- Lager, Erik LU ; Nilsson, Jakob LU ; Østergaard Nielsen, Elsebet ; Nielsen, Mogens ; Liljefors, Tommy and Sterner, Olov LU
- organization
- publishing date
- 2008
- 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
- pmid:18541432
- ISSN
- 0968-0896
- DOI
- 10.1016/j.bmc.2008.05.049
- 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
- 17947d01-3080-411d-be57-61abe6ff18ec (old id 1214985)
- date added to LUP
- 2016-04-01 11:56:41
- date last changed
- 2022-01-26 20:32:51
@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}}, keywords = {{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}}, doi = {{10.1016/j.bmc.2008.05.049}}, volume = {{16}}, year = {{2008}}, }