FXR agonist activity of conformationally constrained analogs of GW 4064.

Adwoa Akwabi-Ameyaw, 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, Derek J Parks, Paul K Spearing, Dan Todd, Shawn P Williams, G Bruce Wisely

Index: Bioorg. Med. Chem. Lett. 19(16) , 4733-9, (2009)

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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.