Liver X receptor agonists with selectivity for LXRbeta; N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropionamides.

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Swahn BM, Macsari I, Viklund J, Ohberg L, Sjodin J, Neelissen J, Lindquist J

Liver X receptor agonists with selectivity for LXRbeta; N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropionamides.

Bioorg Med Chem Lett. 2009 Apr 1;19(7):2009-12. doi: 10.1016/j.bmcl.2009.02.039. Epub 2009 Feb 13.

PubMed ID

19264481 [ View in PubMed

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Abstract

The synthesis and SAR of a new series of LXR agonist is reported. The N-Aryl-3,3,3-trifluoro-2-hydroxy-2-methyl-propionamide hits were found in a limited screen of the AstraZeneca compound collection. The effort to optimize these hits into LXRbeta selectivity is described. Compound 20 displayed desirable pharmacokinetic profile and up regulation of ABCA1 and ABCG1 mRNA in the brain were achieved when evaluated in vivo in mice.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
TO-901317	Oxysterols receptor LXR-alpha	EC 50 (nM)	10	N/A	N/A	Details
TO-901317	Oxysterols receptor LXR-alpha	EC 50 (nM)	85	N/A	N/A	Details