Abstract
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.
MeSH terms
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Animals
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Cell Line
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Humans
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In Vitro Techniques
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Ligands
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Male
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Mice
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Microsomes, Liver / drug effects
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Microsomes, Liver / metabolism
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Patch-Clamp Techniques
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Protein Subunits / physiology
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Pyridazines / chemical synthesis*
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Pyridazines / pharmacokinetics
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Pyridazines / pharmacology
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptors, GABA-A / drug effects*
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Receptors, GABA-A / physiology
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
Substances
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Ligands
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Protein Subunits
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Pyridazines
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Receptors, GABA-A
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Recombinant Proteins