title: Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators.
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 TGR5 agonist. Chemical modifications of this compound resulted in the disclosure of 6α-ethyl-16-epi-avicholic acid that shows enhanced potency at TGR5 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 6α-ethyl-16-epi-avicholic acid as compared to naturally occurring bile acids is reported and discussed.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia , Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pellicciari
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia , Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Antimo
authors.initials: A
authors.lastname: Gioiello
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia , Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Sabbatini
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia , Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Venturoni
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia , Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Nuti
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Alma Mater Studiorum, Università di Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Colliva
authors.affiliation: Intercept Pharmaceuticals , New York, New York 10013, United States.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rizzo
authors.affiliation: Intercept Pharmaceuticals , New York, New York 10013, United States.
authors.forename: Luciano
authors.initials: L
authors.lastname: Adorini
authors.affiliation: Intercept Pharmaceuticals , New York, New York 10013, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Pruzanski
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Alma Mater Studiorum, Università di Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Roda
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia , Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
keywords: 16-epi-avicholic acid; CMC; FXR; TGR5; avicholic acid; bile acid; structure−activity relationship