Synthesis of 4-(3-biaryl)quinoline sulfones as potent liver X receptor agonists

Bioorg Med Chem Lett 20(9):5 (2010) PMID 20382019

A series of 4-(3-biaryl)quinolines with sulfone substituents on the terminal aryl ring (8) was prepared as potential LXR agonists. High affinity LXR@b ligands with generally modest binding selectivity over LXR@a and excellent agonist potency in LXR functional assays were identified. Many compounds had LXR@b binding IC"5"0 values <1.0nM in an ABCA1 mRNA induction assay in J774 mouse cells with efficacy comparable to T0901317. Sulfone 8a was further evaluated in LDL (-/-) mice and shown to reduce atherosclerotic lesion progression.