%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 2325 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