Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile acids from diverse animal species has led to the identification of avicholic acid as a selective but weak TGRS agonist. Chemical modifications of this compound resulted in the disclosure of 6 alpha-ethyl-16-epi-avicholic acid that shows enhanced potency at TGRS and FXR receptors. The synthesis, biological appraisals, and structure-activity relationships of this series of compounds are herein described. Moreover, a thorough physicochemical characterization of 6 alpha-ethyl-16-epi-avicholic acid as compared to naturally occurring bile acids is reported and discussed.
Pellicciari R., Gioiello A., Sabbatini P., Venturoni F., Nuti R., Colliva C., et al. (2012). Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators. ACS MEDICINAL CHEMISTRY LETTERS, 3(4), 273-277 [10.1021/ml200256d].
Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators
COLLIVA, CAROLINA;RODA, ALDO;
2012
Abstract
Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile acids from diverse animal species has led to the identification of avicholic acid as a selective but weak TGRS agonist. Chemical modifications of this compound resulted in the disclosure of 6 alpha-ethyl-16-epi-avicholic acid that shows enhanced potency at TGRS and FXR receptors. The synthesis, biological appraisals, and structure-activity relationships of this series of compounds are herein described. Moreover, a thorough physicochemical characterization of 6 alpha-ethyl-16-epi-avicholic acid as compared to naturally occurring bile acids is reported and discussed.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
