Abstract
2,3-Diarylpyrazolo[1,5-a]pyrimidines are estrogen receptor (ER) antagonists of modest potency that we have described previously. Guided by the crystal structure of an ER-ligand complex that we have obtained with one of these compounds, we prepared analogs that contain a basic side chain at the 2- or 3-aryl group and quickly found one that, according to the structure-based prediction, shows an increase in binding affinity and antagonist potency and a loss of residual agonist activity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Cell Line, Tumor
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Crystallography, X-Ray
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Estrogen Receptor alpha / antagonists & inhibitors*
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Estrogen Receptor alpha / chemistry
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Estrogen Receptor beta / antagonists & inhibitors*
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Humans
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Ligands
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Models, Molecular
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Molecular Structure
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Radioligand Assay
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Structure-Activity Relationship
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Transcriptional Activation
Substances
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Ligands
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Pyrazoles
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Pyrimidines