Abstract
A series of 23 N-(Pyridin-3-yl)benzamides was synthesized and evaluated for their potential to inhibit human steroid-11β-hydroxylase (CYP11B1) and human aldosterone synthase (CYP11B2). The most potent and selective CYP11B2 inhibitors (IC(50) values 53-166 nM) were further evaluated for their potential to inhibit human CYP17 and CYP19, and no inhibition was observed. Clear evidence was shown for N-(Pyridin-3-yl)benzamides to be a highly selective class of CYP11B2 inhibitors in vitro.
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MeSH terms
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Aromatase / chemistry
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Aromatase / metabolism
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Benzamides / chemical synthesis
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Benzamides / chemistry*
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Benzamides / pharmacology
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Cytochrome P-450 CYP11B2 / antagonists & inhibitors*
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Cytochrome P-450 CYP11B2 / 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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Steroid 11-beta-Hydroxylase / antagonists & inhibitors
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Steroid 11-beta-Hydroxylase / metabolism
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Steroid 17-alpha-Hydroxylase / antagonists & inhibitors
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Steroid 17-alpha-Hydroxylase / metabolism
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Structure-Activity Relationship
Substances
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Benzamides
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Enzyme Inhibitors
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Aromatase
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Steroid 17-alpha-Hydroxylase
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Cytochrome P-450 CYP11B2
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Steroid 11-beta-Hydroxylase