Abstract
Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the syntheses of cyclopentanone and cyclohexanone intermediates for SAR studies of the C-ring on the benzopyran scaffold. Modification of the C-ring disrupts binding to ERalpha, thus improving ERbeta selectivity up to 100-fold. X-ray cocrystal structures confirm previously observed binding modes.
MeSH terms
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Animals
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Benzopyrans / chemistry
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Benzopyrans / pharmacology*
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Chemistry, Pharmaceutical / methods*
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Crystallography, X-Ray / methods
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Cyclohexanones / chemical synthesis*
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Cyclohexanones / pharmacology
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Cyclopentanes / chemical synthesis*
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Cyclopentanes / pharmacology
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Drug Design
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Estrogen Receptor beta / agonists*
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Humans
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Ligands
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Mice
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Models, Chemical
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Protein Binding
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Selective Estrogen Receptor Modulators / chemical synthesis*
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Selective Estrogen Receptor Modulators / pharmacology*
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Structure-Activity Relationship
Substances
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Benzopyrans
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Cyclohexanones
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Cyclopentanes
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Estrogen Receptor beta
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Ligands
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Selective Estrogen Receptor Modulators
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cyclopentanone
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cyclohexanone