2. Academic Validation
  3. Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064

Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064

  • Bioorg Med Chem Lett. 2008 Aug 1;18(15):4339-43. doi: 10.1016/j.bmcl.2008.06.073.
Adwoa Akwabi-Ameyaw 1,  Jonathan Y Bass,  Richard D Caldwell,  Justin A Caravella,  Lihong Chen,  Katrina L Creech,  David N Deaton,  Stacey A Jones,  Istvan Kaldor,  Yaping Liu,  Kevin P Madauss,  Harry B Marr,  Robert B McFadyen,  Aaron B Miller,  Frank Navas III,  Derek J Parks,  Paul K Spearing,  Dan Todd,  Shawn P Williams,  G Bruce Wisely
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, GlaxoSmithKline, 5 Moore Drive, PO Box 13398, Research Triangle Park, NC 27709, USA.
PMID: 18621523 DOI: 10.1016/j.bmcl.2008.06.073
Abstract

Starting from the known FXR Agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR Agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.

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