Journal of Medicinal Chemistry · 2005 · 15 citations · 15 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryStructure-activity RelationshipsChemical Library DesignHit-to-lead OptimizationLead Compound DesignLead DiscoveryLigand BindingReceptor-ligand InteractionsFunctional SelectivityGaba AgonistsGaba-a Receptor PharmacologyGabaergic Drug DiscoveryPyridazine ChemistrySelectivityStructure-based Lead DiscoveryStructure-based Ligand Design
Screening of the Merck compound collection identified 6 as an unusually simple, low molecular weight hit with moderate affinity for GABAA receptors. The structural novelty of 6, compared to our advanced series of GABAA alpha5 inverse agonists, made it an attractive molecule for further exploration. This paper will describe the evolution of 6 into a new series of ligands with nanomolar affinity and functional selectivity for GABAA alpha5 receptor subtypes.
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Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology
Dolan B. Pritchett, Harald Sontheimer, Brenda D. Shivers et al. · Nature · 1989 · 1.3K citations
Medicine, Neuroscience, Pharmacology +12
Neil Collinson, Frederick M. Kuenzi, Wolfgang Jarolimek et al. · Journal of Neuroscience · 2002 · 629 citations · Full text