Abstract
There is increasing evidence that compounds with selectivity for gamma-aminobutyric acid(A) (GABA(A)) alpha2- and/or alpha3-subtypes may retain the desirable anxiolytic activity of nonselective benzodiazepines but possess an improved side effect profile. Herein we describe a novel series of GABA(A) alpha2/alpha3 subtype-selective agonists leading to the identification of the development candidate 17, a nonsedating anxiolytic in preclinical animal assays.
MeSH terms
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Animals
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Anti-Anxiety Agents / chemical synthesis*
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Anti-Anxiety Agents / chemistry
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Anti-Anxiety Agents / pharmacology
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Binding, Competitive
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Cell Line
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Dogs
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GABA-A Receptor Agonists*
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GABA-A Receptor Antagonists
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Half-Life
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Humans
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Hypnotics and Sedatives / chemical synthesis*
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Hypnotics and Sedatives / chemistry
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Hypnotics and Sedatives / pharmacology
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Mice
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Oocytes / drug effects
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Oocytes / physiology
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Patch-Clamp Techniques
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Primates
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacology
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Radioligand Assay
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Rats
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Receptors, GABA-A / physiology
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Recombinant Proteins / agonists
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Structure-Activity Relationship
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology
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Xenopus
Substances
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7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo(4,3-b)pyridazine
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Anti-Anxiety Agents
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GABA-A Receptor Agonists
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GABA-A Receptor Antagonists
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GABRA1 protein, human
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GABRA2 protein, human
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GABRA3 protein, human
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Gabra1 protein, mouse
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Gabra3 protein, mouse
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Hypnotics and Sedatives
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Pyridazines
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Receptors, GABA-A
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Recombinant Proteins
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Triazoles