2. Academic Validation
  3. 4-(3-aryloxyaryl)quinoline alcohols are liver X receptor agonists

4-(3-aryloxyaryl)quinoline alcohols are liver X receptor agonists

  • Bioorg Med Chem. 2009 Dec 1;17(23):8086-92. doi: 10.1016/j.bmc.2009.10.001.
Ronald C Bernotas 1,  David H Kaufman,  Robert R Singhaus,  John Ullrich,  Rayomand Unwalla,  Elaine Quinet,  Ponnal Nambi,  Anna Wilhelmsson,  Annika Goos-Nilsson,  Jay Wrobel
Affiliations

Affiliation

  • 1 Chemical Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA. bernotr@wyeth.com
PMID: 19853462 DOI: 10.1016/j.bmc.2009.10.001
Abstract

A series of 4-(3-aryloxyaryl)quinolines with alcohol substituents on the terminal aryl ring was prepared as potential LXR agonists, in which an alcohol group replaced an amide in previously reported amide analogs. High affinity LXR ligands with excellent agonist potency and efficacy in a functional model of LXR activity were identified, demonstrating that alcohols can substitute for amides while retaining LXR activity. The most potent compound was 5b which had an IC(50)=3.3 nM for LXRbeta binding and EC(50)=12 nM (122% efficacy relative to T0901317) in an ABCA1 mRNA induction assay in J774 mouse cells.

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