2. Academic Validation
  3. Quinoline-3-carboxamide containing sulfones as liver X receptor (LXR) agonists with binding selectivity for LXRbeta and low blood-brain penetration

Quinoline-3-carboxamide containing sulfones as liver X receptor (LXR) agonists with binding selectivity for LXRbeta and low blood-brain penetration

  • Bioorg Med Chem Lett. 2010 Jan 15;20(2):689-93. doi: 10.1016/j.bmcl.2009.11.062.
Baihua Hu 1,  Ron Bernotas,  Rayomand Unwalla,  Michael Collini,  Elaine Quinet,  Irene Feingold,  Annika Goos-Nilsson,  Anna Wilhelmsson,  Ponnal Nambi,  Mark Evans,  Jay Wrobel
Affiliations

Affiliation

  • 1 Chemical Science, Collegeville, PA, USA. hub@wyeth.com
PMID: 19962892 DOI: 10.1016/j.bmcl.2009.11.062
Abstract

A series of quinoline-3-carboxamide containing sulfones was prepared and found to have good binding affinity for LXRbeta and moderate binding selectivity over LXRalpha. The 8-Cl quinoline analog 33 with a high TPSA score, displayed 34-fold binding selectivity for LXRbeta over LXRalpha (LXRbeta IC(50)=16nM), good activity for inducing ABCA1 gene expression in a THP macrophage cell line, desired weak potency in the LXRalpha Gal4 functional assay, and low blood-brain barrier penetration in rat.

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