Abstract
A novel series of hexafluorocarbinols were discovered as potent activators of the liver X receptor-alpha using a fluorescence polarization assay. Structure-activity relationship study led to the identification of compounds that are more potent agonists than the endogenous ligand, 24(S), 25-epoxycholesterol, with similar efficacy. Several compounds, including T0901317, were shown to have desirable pharmacokinetic profiles suitable for in vivo studies.
MeSH terms
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Administration, Oral
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Animals
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Cholesterol / analogs & derivatives
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Cholesterol / metabolism
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DNA-Binding Proteins / agonists*
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Fluorescence Polarization
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Hydrocarbons, Fluorinated
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Ligands
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Liver X Receptors
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Male
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Molecular Structure
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Orphan Nuclear Receptors
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear / agonists*
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Structure-Activity Relationship
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Sulfonamides / chemistry*
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Sulfonamides / pharmacokinetics
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Sulfonamides / pharmacology*
Substances
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DNA-Binding Proteins
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Hydrocarbons, Fluorinated
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Ligands
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Liver X Receptors
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Nr1h3 protein, rat
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Orphan Nuclear Receptors
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Receptors, Cytoplasmic and Nuclear
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Sulfonamides
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T0901317
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24,25-epoxycholesterol
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Cholesterol