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.
Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators / Pellicciari R.; Gioiello A.; Sabbatini P.; Venturoni F.; Nuti R.; Colliva C.; Rizzo G.; Adorini L.; Pruzanski M.; Roda A.; Macchiarulo A.. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - STAMPA. - 3:4(2012), pp. 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.
