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

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.
Britt-Marie Swahn 1,  Istvan Macsari,  Jenny Viklund,  Liselotte Ohberg,  Johanna Sjödin,  Jan Neelissen,  Johanna Lindquist
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden. britt-marie.swahn@astrazeneca.com
PMID: 19264481 DOI: 10.1016/j.bmcl.2009.02.039
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.

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