FXR agonist activity of conformationally constrained analogs of GW 4064

  • Bioorg Med Chem Lett. 2009 Aug 15;19(16):4733-9. doi: 10.1016/j.bmcl.2009.06.062.
Adwoa Akwabi-Ameyaw  1 ,  Jonathan Y Bass ,  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 ,  Frank Navas 3rd ,  Derek J Parks ,  Paul K Spearing ,  Dan Todd ,  Shawn P Williams ,  G Bruce Wisely
Affiliations
  • 1. Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
PMID: 19586769 DOI: 10.1016/j.bmcl.2009.06.062
Abstract

Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.