4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists

A series of 4-(3-aryloxyaryl)quinolines with sulfone substituents on the terminal aryl ring (7) was prepared as LXR agonists. High affinity LXR ligands with excellent agonist potency and efficacy in functional assays of LXR activity were identified. In general, these sulfone agonists were equal to or superior to previously described alcohol and amide analogs in terms of affinity, functional potency, and microsomal stability. Many of the sulfones had LXRβ binding IC50 values <10 nM while the most potent compounds in an ABCA1 mRNA induction assay in J774 mouse cells had EC50 values <10 nM and were as efficacious as T0901317.

Graphical abstractA series of 4-(3-aryloxyaryl)quinoline sulfones 7 was prepared as LXR agonists.Figure optionsDownload full-size imageDownload as PowerPoint slide