title: Extending SAR of bile acids as FXR ligands: discovery of 23-N-(carbocinnamyloxy)-3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-amine.
abstract: Within our efforts in the discovery of novel potent and selective ligands for the FXR receptor, 23-N-(carbocinnamyloxy)-3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-amine was synthesized and evaluated for its ability to activate and modulate the biological response of the receptor. Alphascreen and RT-PCR revealed that the 6α-ethyl-24-norcholanyl-23-amine derivate behaves as full FXR agonist endowed with high binding affinity and efficacy, representing a promising lead candidate for further optimization. In addition, docking studies provide new insights into the molecular basis governing the partial and full agonist activity at FXR.
authors: Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Perugia, Italy.
authors: Antimo
authors: A
authors: Gioiello
authors: Antonio
authors: A
authors: Macchiarulo
authors: Andrea
authors: A
authors: Carotti
authors: Paolo
authors: P
authors: Filipponi
authors: Gabriele
authors: G
authors: Costantino
authors: Giovanni
authors: G
authors: Rizzo
authors: Luciano
authors: L
authors: Adorini
authors: Roberto
authors: R
authors: Pellicciari
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry*; D003198:Computer Simulation; D055808:Drug Discovery; D005765:Gastrointestinal Agents; D008024:Ligands; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D005765:Gastrointestinal Agents; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated