Abstract
Pyrrole[2,3-d]azepines have been identified as potent agonists of the farnesoid X receptor (FXR). Based on the planar X-ray crystal structure of WAY-362450 1 in the ligand binding domain and molecular modeling studies, non-planar reduced compounds were designed which led to agonists that exhibit high aqueous solubility and retain moderate in vitro potency.
MeSH terms
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Azepines / chemistry
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Azepines / pharmacology*
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Humans
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Models, Molecular
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Protein Binding
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Pyrroles / chemistry
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Pyrroles / pharmacology*
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Receptors, Cytoplasmic and Nuclear / agonists*
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Receptors, Cytoplasmic and Nuclear / chemistry
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Structure-Activity Relationship
Substances
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Azepines
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Pyrroles
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Receptors, Cytoplasmic and Nuclear
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farnesoid X-activated receptor