Abstract
A library of small tetrahydroisoquinoline ligands, previously identified via structure- and chemistry-based hierarchical organization of library scaffolds in tree-like arrangements, has been generated as novel estrogen receptor agonistic fragments via traditional medicinal chemistry exploration. The approach described has allowed for the rapid evaluation of a structure-activity relationship of the ligands concerning estrogen receptor affinity and estrogen receptor β subtype selectivity. The structural biological insights obtained from the fragments aid the understanding of larger analogues and constitute attractive starting points for further optimization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Drug Design*
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Estrogen Receptor alpha / agonists
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Estrogen Receptor alpha / antagonists & inhibitors
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Estrogen Receptor alpha / chemistry
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Estrogen Receptor alpha / metabolism*
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Estrogen Receptor beta / agonists
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Estrogen Receptor beta / antagonists & inhibitors
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Estrogen Receptor beta / chemistry
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Estrogen Receptor beta / metabolism*
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Ligands
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Models, Molecular
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Protein Structure, Tertiary
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / metabolism
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Small Molecule Libraries / pharmacology
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Substrate Specificity
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Tetrahydroisoquinolines / chemistry*
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Tetrahydroisoquinolines / metabolism*
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Tetrahydroisoquinolines / pharmacology
Substances
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Ligands
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Small Molecule Libraries
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Tetrahydroisoquinolines
Associated data
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PDB/3OMO
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PDB/3OMP
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PDB/3OMQ