Conformationally constrained farnesoid X receptor (FXR) agonists: alternative replacements of the stilbene

  • Bioorg Med Chem Lett. 2011 Oct 15;21(20):6154-60. doi: 10.1016/j.bmcl.2011.08.034.
Adwoa Akwabi-Ameyaw  1 ,  Justin A Caravella ,  Lihong Chen ,  Katrina L Creech ,  David N Deaton ,  Kevin P Madauss ,  Harry B Marr ,  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: 21890356 DOI: 10.1016/j.bmcl.2011.08.034
Abstract

To further explore the optimum placement of the acid moiety in conformationally constrained analogs of GW 4064 1a, a series of stilbene replacements were prepared. The benzothiophene 1f and the indole 1g display the optimal orientation of the carboxylate for enhanced FXR agonist potency.