1442467-75-5Relevant academic research and scientific papers
Asymmetric synthesis of the four diastereoisomers of a novel non-steroidal farnesoid X receptor (FXR) agonist: Role of the chirality on the biological activity
Marinozzi, Maura,Carotti, Andrea,Sardella, Roccaldo,Buonerba, Federica,Ianni, Federica,Natalini, Benedetto,Passeri, Daniela,Rizzo, Giovanni,Pellicciari, Roberto
, p. 3780 - 3789 (2013/07/19)
An asymmetric synthetic strategy was designed for the preparation of the four possible diastereoisomers of 3,6-dimethyl-1-(2-methylphenyl)-4-(4- phenoxyphenyl)-4,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-one, a non-steroidal FXR agonist, we recently discovered following a virtual screening approach. The results obtained from an AlphaScreen assay clearly demonstrated that only the isomer endowed with 4R,6S absolute configuration is responsible for the biological activity. A deep investigation of the different putative binding modes adopted by these enantiomerically pure ligands using computational modeling studies confirmed the enantioselectivity of FXR towards this class of molecules.
