2. Academic Validation
  3. The discovery of tertiary-amine LXR agonists with potent cholesterol efflux activity in macrophages

The discovery of tertiary-amine LXR agonists with potent cholesterol efflux activity in macrophages

  • Bioorg Med Chem Lett. 2009 Oct 1;19(19):5617-21. doi: 10.1016/j.bmcl.2009.08.036.
Joseph P Marino Jr 1,  Lara S Kallander,  Chun Ma,  Hye-Ja Oh,  Dennis Lee,  Dimitri E Gaitanopoulos,  John A Krawiec,  Derek J Parks,  Christine L Webb,  Kelly Ziegler,  Michael Jaye,  Scott K Thompson
Affiliations

Affiliation

  • 1 Chemistry, Metabolic Pathways Centre for Excellence in Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, United States. joseph.p.marino@gsk.com
PMID: 19717304 DOI: 10.1016/j.bmcl.2009.08.036
Abstract

The liver X receptors (LXR) play a key role in Cholesterol homeostasis and lipid metabolism. SAR studies around tertiary-amine lead molecule 2, an LXR full agonist, revealed that steric and conformational changes to the acetic acid and propanolamine groups produce dramatic effects on agonist efficacy and potency. The new analogs possess good functional activity, demonstrating the ability to upregulate LXR target genes, as well as promote Cholesterol efflux in macrophages.

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