Abstract
A series of potent and selective adamantane aminoamide 11-beta-HSD-1 inhibitors has been optimized. Chemically these studies were expedited by utilizing readily obtained amino acids as starting materials or an isocyanide multicomponent reaction. Structure-activity relationship studies resulted in the discovery of dual human and mouse 11-beta-HSD-1 potent and selective inhibitors like adamantane 11 and related compounds with high metabolic stability and robust pharmacokinetic profiles.
MeSH terms
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
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11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
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11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors
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11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
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Adamantane / chemical synthesis*
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Adamantane / chemistry
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Adamantane / pharmacokinetics
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Adamantane / pharmacology*
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Animals
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Cyanides / chemistry*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Humans
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Mice
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Molecular Structure
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Structure-Activity Relationship
Substances
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Cyanides
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Enzyme Inhibitors
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11-beta-Hydroxysteroid Dehydrogenase Type 1
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11-beta-Hydroxysteroid Dehydrogenase Type 2
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Adamantane