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.

A 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 as PowerPoint slide