%0 Journal Article
%A Lager, Erik
%A Andersson, Pierre
%A Nilsson, Jakob
%A Pettersson, Ingrid
%A Nielsen, Elsebet Østergaard
%A Nielsen, Mogens
%A Sterner, Olov
%A Liljefors, Tommy
%D 2006
%T 4-Quinolone Derivatives: High-Affinity Ligands at the Benzodiazepine Site of Brain GABAA
Receptors. Synthesis, Pharmacology, and Pharmacophore Modeling
%U https://acs.figshare.com/articles/journal_contribution/4_Quinolone_Derivatives_High_Affinity_Ligands_at_the_Benzodiazepine_Site_of_Brain_GABA_sub_A_sub_Receptors_Synthesis_Pharmacology_and_Pharmacophore_Modeling/3226255
%R 10.1021/jm058057p.s001
%2 https://acs.figshare.com/ndownloader/files/5060320
%K α 1 subunit
%K receptor
%K α 1 β 2 γ 2 S
%K compound
%K graphics Modelling 2004
%K benzodiazepine site
%K α 3 β 2 γ 2 S GABA
%X The 3-ethoxycarbonyl-4-quinolone compound 1 has previously been identified via a database search as an
interesting lead compound for ligand binding at the benzodiazepine site of GABAA 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 α1β2γ2S
and α3β2γ2S GABAA receptor subtypes, and two of the compounds (5 and 19) display selectivity for α1-
versus α3-containing receptors by a factor of 22 and 27, respectively. This selectivity for α1β2γ2S is in the
same range as that for the well-known α1 subunit selective compound zolpidem.
%I ACS Publications