title: Exploring subtype selectivity and metabolic stability of a novel series of ligands for the benzodiazepine binding site of the GABAA receptor.
abstract: A novel series of agonists at the benzodiazepine binding site of the GABA(A) receptor was prepared by functionalizing a known template. Adding substituents to the pyrazolone-oxygen of CGS-9896 led to a number of compounds with selectivities for either α2- or α1-containing GABA(A) receptor subtypes offering an entry into indications such as anxiety and insomnia. In this communication, structure-activity relationship and efforts to increase in vitro stabilities are discussed.
authors.affiliation: Novartis Institutes for BioMedical Research, Neuroscience Research, Basel, Switzerland. samuel.hintermann@novartis.com
authors.forename: Samuel
authors.initials: S
authors.lastname: Hintermann
authors.forename: Konstanze
authors.initials: K
authors.lastname: Hurth
authors.forename: Joachim
authors.initials: J
authors.lastname: Nozulak
authors.forename: Marina
authors.initials: M
authors.lastname: Tintelnot-Blomley
authors.forename: Reiner
authors.initials: R
authors.lastname: Aichholz
authors.forename: Joachim
authors.initials: J
authors.lastname: Blanz
authors.forename: Klemens
authors.initials: K
authors.lastname: Kaupmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Mosbacher
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D004355:Drug Stability; D058785:GABA-A Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058785:GABA-A Receptor Agonists; D008024:Ligands; D011720:Pyrazoles; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C034704:2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one