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

• Published in: Bioorganic & medicinal chemistry letters 2010, Vol.20 (1), p.209-212
• Main Authors: Bernotas, Ronald C., Singhaus, Robert R., Kaufman, David H., Travins, Jeremy M., Ullrich, John W., Unwalla, Rayomand, Quinet, Elaine, Evans, Mark, Nambi, Ponnal, Olland, Andrea, Kauppi, Björn, Wilhelmsson, Anna, Goos-Nilsson, Annika, Wrobel, Jay
• Format: Article
• Language: English
• Subjects: ABCA1; Animals; Atherosclerosis; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Binding Sites; Biological and medical sciences; Cell Line; Cholesterol; Computer Simulation; General and cellular metabolism. Vitamins; Humans; Hydrocarbons, Fluorinated - chemistry; Hydrocarbons, Fluorinated - pharmacology; Hydrogen Bonding; Lipid; Liver X receptor; Liver X Receptors; LXR; Medical sciences; Mice; Microsomes, Liver - metabolism; Orphan Nuclear Receptors - agonists; Orphan Nuclear Receptors - metabolism; Pharmacology. Drug treatments; Quinoline; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Rats; Structure-Activity Relationship; Sulfonamides - chemistry; Sulfonamides - pharmacology; Sulfone; Sulfones - chemical synthesis; Sulfones - chemistry; Sulfones - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.10.132

A series of 4-(3-aryloxyaryl)quinoline sulfones 7 was prepared as LXR 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 IC 50 values