Abstract
High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11beta-Hydroxysteroid Dehydrogenase Type 1 (11beta-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11beta-HSD1 IC(50)=3nM).
MeSH terms
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
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Animals
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Binding Sites / drug effects
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Crystallography, X-Ray
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Mice
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Models, Molecular
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Molecular Structure
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Molecular Weight
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Piperazines / chemical synthesis
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Piperazines / chemistry
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Piperazines / pharmacology*
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Small Molecule Libraries
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Stereoisomerism
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Structure-Activity Relationship
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Sulfhydryl Compounds / chemical synthesis
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / pharmacology*
Substances
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Enzyme Inhibitors
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Piperazines
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Small Molecule Libraries
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Sulfhydryl Compounds
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11-beta-Hydroxysteroid Dehydrogenase Type 1