Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene

  • Bioorg Med Chem Lett. 2011 Feb 15;21(4):1206-13. doi: 10.1016/j.bmcl.2010.12.089.
Jonathan Y Bass  1 ,  Justin A Caravella ,  Lihong Chen ,  Katrina L Creech ,  David N Deaton ,  Kevin P Madauss ,  Harry B Marr ,  Robert B McFadyen ,  Aaron B Miller ,  Wendy Y Mills ,  Frank Navas 3rd ,  Derek J Parks ,  Terrence L Smalley Jr ,  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: 21256005 DOI: 10.1016/j.bmcl.2010.12.089
Abstract

To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes.

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