10.1021/jm058057p.s001
Erik Lager
Erik
Lager
Pierre Andersson
Pierre
Andersson
Jakob Nilsson
Jakob
Nilsson
Ingrid Pettersson
Ingrid
Pettersson
Elsebet Østergaard Nielsen
Elsebet Østergaard
Nielsen
Mogens Nielsen
Mogens
Nielsen
Olov Sterner
Olov
Sterner
Tommy Liljefors
Tommy
Liljefors
4-Quinolone Derivatives: High-Affinity Ligands at the Benzodiazepine Site of Brain GABA<sub>A</sub>
Receptors. Synthesis, Pharmacology, and Pharmacophore Modeling
American Chemical Society
2006
α 1 subunit
receptor
α 1 β 2 γ 2 S
compound
graphics Modelling 2004
benzodiazepine site
α 3 β 2 γ 2 S GABA
2006-04-20 00:00:00
Journal contribution
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
The 3-ethoxycarbonyl-4-quinolone compound <b>1</b> has previously been identified via a database search as an
interesting lead compound for ligand binding at the benzodiazepine site of GABA<sub>A</sub> receptors (Kahnberg et
al. <i>J. Mol. Graphics Modelling </i><b>2004</b>, <i>23</i>, 253−261). Pharmacophore-guided optimization of this lead
compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds <b>20</b>
and <b>23</b>−<b>25 </b>displaying sub-nanomolar affinities. A few of the compounds have been tested on the α<sub>1</sub>β<sub>2</sub>γ<sub>2S</sub>
and α<sub>3</sub>β<sub>2</sub>γ<sub>2S</sub> GABA<sub>A</sub> receptor subtypes, and two of the compounds (<b>5</b> and <b>19</b>) display selectivity for α<sub>1</sub>-
versus α<sub>3</sub>-containing receptors by a factor of 22 and 27, respectively. This selectivity for α<sub>1</sub>β<sub>2</sub>γ<sub>2S</sub> is in the
same range as that for the well-known α<sub>1</sub> subunit selective compound zolpidem.