Abstract
Inhibition of 11beta-HSD1 has demonstrated potential in the treatment of various components of metabolic syndrome. We wish to report herein the discovery of novel azabicyclic sulfonamide based 11beta-HSD1 inhibitors. Highly potent compounds exhibiting inhibitory activities at both human and mouse 11beta-HSD1 were identified. Several compounds demonstrated significant in vivo activity in the mouse cortisone challenge assay.
Copyright 2010 Elsevier Ltd. All rights reserved.
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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Animals
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Azabicyclo Compounds / chemistry*
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Cortisone / chemistry
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Cortisone / metabolism
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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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Hypoglycemic Agents / chemical synthesis
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Hypoglycemic Agents / chemistry*
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Hypoglycemic Agents / pharmacology
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Mice
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology
Substances
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Azabicyclo Compounds
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Enzyme Inhibitors
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Hypoglycemic Agents
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Sulfonamides
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11-beta-Hydroxysteroid Dehydrogenase Type 1
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Cortisone