Abstract
New 3-aryl-6-(3-thienyl)pyrazolo[1,5-a]pyrimidin-7-ones (2a-j) are synthesized and evaluated in vitro on Bz/GABA(A) receptors and on recombinant benzodiazepine receptors (alpha x beta 2/3 gamma 2; x = 1-3, 5) expressed in HEK293 cells. SAR studies on the new compounds are conducted and molecular modeling is accomplished to better investigate requirements leading to subtype selectivity. Some of the synthesized compounds are tested in vivo to explore their pharmacological effect as a consequence of their high alpha 1 beta 2 gamma 2 subtype selectivity observed in vitro.
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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Anticonvulsants / chemical synthesis
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Anticonvulsants / chemistry
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Anticonvulsants / pharmacology
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Binding, Competitive
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Brain / metabolism
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Cattle
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In Vitro Techniques
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Ligands
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Models, Molecular
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Muscle Relaxants, Central / chemical synthesis
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Muscle Relaxants, Central / chemistry
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Muscle Relaxants, Central / pharmacology
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Quantitative Structure-Activity Relationship
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Receptors, GABA-A / drug effects*
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Receptors, GABA-A / metabolism
Substances
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Anti-Anxiety Agents
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Anticonvulsants
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Ligands
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Muscle Relaxants, Central
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Pyrimidines
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Receptors, GABA-A