Abstract
In the continuation of our 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor research, cyclic sulfonamide derivatives with an acetamide group at the 2-position were synthesized and evaluated for their abilities to inhibit 11β-HSD1. Among this series, Compound 34 showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, good pharmacokinetic and safety profiles human ether-a-go-go related gene (hERG and cytochrome P450 (CYP)). Also, a docking study explained the activity difference between human and mouse 11β-HSD1.
Publication types
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Research Support, Non-U.S. Gov't
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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Acetamides / chemistry*
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Animals
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Cytochrome P-450 Enzyme Inhibitors
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Cytochrome P-450 Enzyme System / metabolism
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ERG1 Potassium Channel
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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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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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Mice
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Sulfonamides / chemistry*
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Thiazines / chemistry*
Substances
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2-(3-benzoyl-4-hydroxy-1,1-dioxido-2H-benzo(e)(1,2)thiazin-2-yl)-N- (3-(trifluoromethyl)phenyl)acetamide
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Acetamides
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Cytochrome P-450 Enzyme Inhibitors
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ERG1 Potassium Channel
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Enzyme Inhibitors
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Ether-A-Go-Go Potassium Channels
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KCNH2 protein, human
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Sulfonamides
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Thiazines
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acetamide
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Cytochrome P-450 Enzyme System
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11-beta-Hydroxysteroid Dehydrogenase Type 1
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11-beta-Hydroxysteroid Dehydrogenase Type 2