Abstract
A series of high-affinity GABA(A) agonists with good oral bioavailability in rat and dog and functional selectivity for the GABA(A)alpha2 and -alpha3 subtypes is reported. The 7-trifluoromethylimidazopyrimidine 14g and the 7-propan-2-olimidazopyrimidine 14k are anxiolytic in both conditioned and unconditioned animal models of anxiety with minimal sedation observed at full BZ binding site occupancy.
MeSH terms
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Administration, Oral
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Animals
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Anxiety Disorders / drug therapy*
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Binding Sites
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Biological Availability
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Cell Line
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Disease Models, Animal
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Dogs
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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GABA-A Receptor Agonists*
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Humans
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Molecular Structure
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Patch-Clamp Techniques
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Pyrimidines / chemical synthesis
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Pyrimidines / pharmacokinetics
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Pyrimidines / pharmacology*
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Rats
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Receptors, GABA-A
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Structure-Activity Relationship
Substances
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GABA-A Receptor Agonists
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GABRA3 protein, human
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Gabra3 protein, rat
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Pyrimidines
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Receptors, GABA-A