2. Academic Validation
  3. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064

Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064

  • Bioorg Med Chem Lett. 2009 Jun 1;19(11):2969-73. doi: 10.1016/j.bmcl.2009.04.047.
Jonathan Y Bass 1,  Richard D Caldwell,  Justin A Caravella,  Lihong Chen,  Katrina L Creech,  David N Deaton,  Kevin P Madauss,  Harry B Marr,  Robert B McFadyen,  Aaron B Miller,  Derek J Parks,  Dan Todd,  Shawn P Williams,  G Bruce Wisely
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
PMID: 19410460 DOI: 10.1016/j.bmcl.2009.04.047
Abstract

Starting from the known FXR Agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

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