Abstract
A series of 4-aryl-5-(4-piperidyl)-3-isoxazolol GABAA antagonists have been synthesized and pharmacologically characterized. The meta-phenyl-substituted compounds 9k and 9m and the para-phenoxy-substituted compound 9l all display high affinities (Ki=10-70 nM) and antagonist potencies in the low nanomolar range (Ki=9-10 nM). These potencies are significantly higher than those of previously reported 4-PIOL antagonists and considerably higher than that of the standard GABAA antagonist SR 95531.
MeSH terms
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Animals
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Female
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GABA-A Receptor Antagonists*
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Humans
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In Vitro Techniques
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Isoxazoles / chemical synthesis*
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Isoxazoles / chemistry
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Isoxazoles / pharmacology
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Models, Molecular
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Molecular Conformation
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Oocytes / drug effects
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Oocytes / physiology
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Patch-Clamp Techniques
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacology
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Structure-Activity Relationship
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Xenopus
Substances
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GABA-A Receptor Antagonists
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Isoxazoles
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Piperidines
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Pyridazines
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gabazine