Abstract
A novel class of adamantane ethers 11beta-hydroxysteroid hydrogenase type I inhibitors has been discovered. These compounds have excellent HSD-1 potency and selectivity against HSD-2. The structure-activity relationships, selectivity, metabolism, PK, ex vivo pharmacodynamic data, and an X-ray crystal structure of one of these inhibitors bound to h-HSD-1 are discussed.
MeSH terms
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics
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Adamantane / analogs & derivatives*
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Adamantane / chemical synthesis
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Adamantane / pharmacology*
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Alkylation
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Animals
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Ethers / chemical synthesis
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Ethers / pharmacology
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Half-Life
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Humans
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Indicators and Reagents
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Mice
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Mice, Knockout
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Microsomes, Liver / enzymology
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Microsomes, Liver / metabolism
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Models, Molecular
Substances
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Enzyme Inhibitors
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Ethers
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Indicators and Reagents
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11-beta-Hydroxysteroid Dehydrogenase Type 1
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Adamantane