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

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Hu B, Bernotas R, Unwalla R, Collini M, Quinet E, Feingold I, Goos-Nilsson A, Wilhelmsson A, Nambi P, Evans M, Wrobel J

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. Epub 2009 Dec 3.

PubMed ID

19962892 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
TO-901317	Oxysterols receptor LXR-alpha	IC 50 (nM)	13	N/A	N/A	Details
TO-901317	Oxysterols receptor LXR-alpha	EC 50 (nM)	140	N/A	N/A	Details