Structural development of tetrachlorophthalimides as liver X receptor β (LXRβ)-selective agonists with improved aqueous solubility

Bioorg Med Chem Lett. 2018 Feb 15;28(4):796-801. doi: 10.1016/j.bmcl.2017.12.024. Epub 2017 Dec 13.

Abstract

LXRβ-selective agonists are promising candidates to improve atherosclerosis without increasing plasma or hepatic TG levels. We have reported a series of tetrachlorophthalimide analogs as an LXRβ-selective agonist. However, they exhibited poor aqueous solubility probably due to its high hydrophobicity and highly rigid and plane structure. In this report, we present further structural development of tetrachloro(styrylphenyl)phthalimides as the LXRβ-selective agonists with improved aqueous solubility.

Keywords: LXR; Liver X receptor; Selective agonist.

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • Animals
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Liver X Receptors / agonists*
  • Mice
  • Molecular Docking Simulation
  • Molecular Structure
  • Phthalimides / chemical synthesis
  • Phthalimides / chemistry
  • Phthalimides / pharmacology*
  • RNA, Messenger / genetics
  • Solubility
  • Structure-Activity Relationship
  • THP-1 Cells
  • Water / chemistry*

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Liver X Receptors
  • Phthalimides
  • RNA, Messenger
  • Water