Abstract
Topical application of CYP11B1 inhibitors to reduce cutaneous cortisol is a novel strategy to promote healing of chronic wounds. Pyridyl substituted arylsulfonyltetrahydroquinolines were designed and synthesized resulting in a strong inhibitor 34 (IC50 = 5 nM). It showed no inhibition of CYP17 and CYP19 and no mutagenic effects. It exhibited inverse metabolic stability in plasma (t1/2 ≫ 150 min), which is similar to wound fluid in composition, and in liver S9 fractions (t1/2 = 16 min).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aromatase / metabolism
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Aromatase Inhibitors / blood
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Aromatase Inhibitors / metabolism
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Aromatase Inhibitors / pharmacology
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Cytochrome P-450 CYP11B2 / antagonists & inhibitors
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Cytochrome P-450 Enzyme Inhibitors / blood
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Cytochrome P-450 Enzyme Inhibitors / metabolism*
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Cytochrome P-450 Enzyme Inhibitors / pharmacology*
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Drug Design*
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Drug Stability
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Humans
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Liver / metabolism*
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Steroid 11-beta-Hydroxylase / antagonists & inhibitors*
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Wound Healing / drug effects*
Substances
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Aromatase Inhibitors
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Cytochrome P-450 Enzyme Inhibitors
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Aromatase
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Cytochrome P-450 CYP11B2
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Steroid 11-beta-Hydroxylase