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. Epub 2009 Nov 23.

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.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacokinetics
  • Cell Line
  • Humans
  • Liver X Receptors
  • Mice
  • Microsomes, Liver / metabolism
  • Orphan Nuclear Receptors / agonists*
  • Orphan Nuclear Receptors / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Structure-Activity Relationship
  • Sulfones / chemistry*

Substances

  • ATP-Binding Cassette Transporters
  • Benzimidazoles
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Sulfones