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4-quinolone derivatives: High-affinity ligands at the benzodiazepine site of brain GABA(A) receptors. synthesis, pharmacology, and pharmacophore modeling

Lager, Erik LU ; Andersson, P ; Nilsson, Jakob LU ; Pettersson, I ; Nielsen, EO ; Nielsen, M ; Sterner, Olov LU and Liljefors, T (2006) In Journal of Medicinal Chemistry 49(8). p.2526-2533
Abstract
The 3-ethoxycarbonyl-4-quinolone compound I has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the alpha(1)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes, and two of the compounds (5 and 19) display selectivity for alpha(1) versus alpha(3)-containing receptors by a factor of 22 and 27, respectively. This selectivity... (More)
The 3-ethoxycarbonyl-4-quinolone compound I has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the alpha(1)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes, and two of the compounds (5 and 19) display selectivity for alpha(1) versus alpha(3)-containing receptors by a factor of 22 and 27, respectively. This selectivity for alpha(1)beta(2)gamma(2s) is in the same range as that for the well-known alpha(1) subunit selective compound zolpidem. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
49
issue
8
pages
2526 - 2533
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:16610795
  • wos:000236979100017
  • scopus:33646076225
ISSN
1520-4804
DOI
10.1021/jm058057p
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
62fc2d58-9fd9-4612-a05a-233937f4b38b (old id 411149)
date added to LUP
2016-04-01 12:06:29
date last changed
2021-10-06 04:13:34
@article{62fc2d58-9fd9-4612-a05a-233937f4b38b,
  abstract     = {The 3-ethoxycarbonyl-4-quinolone compound I has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the alpha(1)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes, and two of the compounds (5 and 19) display selectivity for alpha(1) versus alpha(3)-containing receptors by a factor of 22 and 27, respectively. This selectivity for alpha(1)beta(2)gamma(2s) is in the same range as that for the well-known alpha(1) subunit selective compound zolpidem.},
  author       = {Lager, Erik and Andersson, P and Nilsson, Jakob and Pettersson, I and Nielsen, EO and Nielsen, M and Sterner, Olov and Liljefors, T},
  issn         = {1520-4804},
  language     = {eng},
  number       = {8},
  pages        = {2526--2533},
  publisher    = {The American Chemical Society (ACS)},
  series       = {Journal of Medicinal Chemistry},
  title        = {4-quinolone derivatives: High-affinity ligands at the benzodiazepine site of brain GABA(A) receptors. synthesis, pharmacology, and pharmacophore modeling},
  url          = {http://dx.doi.org/10.1021/jm058057p},
  doi          = {10.1021/jm058057p},
  volume       = {49},
  year         = {2006},
}