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
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.