1-(3-Aryloxyaryl)benzimidazole sulfones are liver X receptor agonists

  • Bioorg Med Chem Lett. 2010 Jan 15;20(2):526-30. doi: 10.1016/j.bmcl.2009.11.099.
Jeremy M Travins  1 ,  Ronald C Bernotas ,  David H Kaufman ,  Elaine Quinet ,  Ponnal Nambi ,  Irene Feingold ,  Christine Huselton ,  Anna Wilhelmsson ,  Annika Goos-Nilsson ,  Jay Wrobel
Affiliations
  • 1. Chemical Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA.
PMID: 20006495 DOI: 10.1016/j.bmcl.2009.11.099
Abstract

A series of 1-(3-aryloxyaryl)benzimidazoles incorporating a sulfone substituent (6) was prepared. High affinity LXR ligands were identified (LXRbeta binding IC(50) values <10nM), some with excellent agonist potency and efficacy in a functional assay of LXR activity measuring ABCA1 mRNA increases in human macrophage THP1 cells. The compounds were typically stable in liver microsome preparations and had good oral exposure in mice.