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

Adwoa Akwabi-Ameyaw; 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

doi:10.1016/j.bmcl.2011.08.034

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. Epub 2011 Aug 11.

Authors

Adwoa Akwabi-Ameyaw¹, 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

Affiliation

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.

MeSH terms

Amino Acid Sequence
Animals
Cell Line
Humans
Isoxazoles / chemistry*
Isoxazoles / pharmacology*
Molecular Conformation
Molecular Sequence Data
Receptors, Cytoplasmic and Nuclear / agonists*
Receptors, Cytoplasmic and Nuclear / metabolism
Stilbenes / chemistry*
Stilbenes / pharmacology*

Substances

Isoxazoles
Receptors, Cytoplasmic and Nuclear
Stilbenes
farnesoid X-activated receptor
GW 4064