Journal of Medicinal Chemistry · 2002 · 731 citations · 11 references
MedicineMedicinal ChemistryPharmacologyBiochemical PharmacologyDrug DiscoveryMolecular PharmacologyBile Acid BiosynthesisBile Acid MetabolismCholestatic Liver InjuryCholesterol MetabolismStructure-activity Relationship AnalysisAnimal Models Of CholestasisBile Acid PharmacologyFarnesoid X Receptor AgonistsFarnesoid X Receptor Signaling
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.
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