Discovery and optimization of a novel series of liver X receptor-α agonists

A novel series of hexafluorocarbinols were discovered as potent activators of the liver X receptor-α using a fluorescence polarization assay. Structure–activity relationship study led to the identification of compounds that are more potent agonists than the endogenous ligand, 24(S), 25-epoxycholesterol, with similar efficacy. Several compounds, including T0901317, were shown to have desirable pharmacokinetic profiles suitable for in vivo studies.

Graphical abstractA novel series of Liver X Receptor-α activators have been synthesized and their receptor activation potentials were evaluated. Compounds with enhanced potency and similar efficacy to those of the endogenous ligands, oxysterols, were identified.Figure optionsDownload full-size imageDownload as PowerPoint slide