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

…, M Collini, E Quinet, I Feingold, A Goos-Nilsson…

Index: Hu, Baihua; Bernotas, Ron; Unwalla, Rayomand; Collini, Michael; Quinet, Elaine; Feingold, Irene; Goos-Nilsson, Annika; Wilhelmsson, Anna; Nambi, Ponnal; Evans, Mark; Wrobel, Jay Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 2 p. 689 - 693

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Citation Number: 16

Abstract

A series of quinoline-3-carboxamide containing sulfones was prepared and found to have good binding affinity for LXRβ and moderate binding selectivity over LXRα. The 8-Cl quinoline analog 33 with a high TPSA score, displayed 34-fold binding selectivity for LXRβ over LXRα (LXRβ IC50= 16nM), good activity for inducing ABCA1 gene expression in a THP macrophage cell line, desired weak potency in the LXRα Gal4 functional assay, and low ...