Abstract
A series of 6alpha-alkyl-substituted analogues of chenodeoxycholic acid (CDCA) were synthesized and evaluated as potential farnesoid X receptor (FXR) ligands. Among them, 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA) was shown to be a very potent and selective FXR agonist (EC(50) = 99 nM) and to be endowed with anticholeretic activity in an in vivo rat model of cholestasis.
MeSH terms
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Animals
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Anticholesteremic Agents / chemical synthesis*
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Anticholesteremic Agents / chemistry
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Anticholesteremic Agents / pharmacology
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Cell Line
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Chenodeoxycholic Acid / analogs & derivatives
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Chenodeoxycholic Acid / chemical synthesis*
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Chenodeoxycholic Acid / chemistry
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Chenodeoxycholic Acid / pharmacology
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Cholestasis / chemically induced
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Cholestasis / drug therapy
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Cholestasis / pathology
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DNA-Binding Proteins / agonists*
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Humans
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Ligands
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Liver / drug effects
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Liver / pathology
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Rats
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Rats, Wistar
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Receptors, Cytoplasmic and Nuclear
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Structure-Activity Relationship
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Transcription Factors / agonists*
Substances
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Anticholesteremic Agents
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DNA-Binding Proteins
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Ligands
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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obeticholic acid
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farnesoid X-activated receptor
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Chenodeoxycholic Acid