Design and synthesis of novel RXR-selective modulators with improved pharmacological profile

  • Bioorg Med Chem Lett. 2003 Nov 17;13(22):4071-5. doi: 10.1016/j.bmcl.2003.08.048.
Pierre-Yves Michellys  1 ,  Marcus F Boehm ,  Jyun-Hung Chen ,  Timothy A Grese ,  Donald S Karanewsky ,  Mark D Leibowitz ,  Sha Liu ,  Dale A Mais ,  Christopher M Mapes ,  Anne Reifel-Miller ,  Katheen M Ogilvie ,  Deepa Rungta ,  Anthony W Thompson ,  John S Tyhonas ,  Nathan Yumibe ,  Robert J Ardecky
Affiliations
  • 1. Department of Medicinal Chemistry, Ligand Pharmaceuticals Incorporated, 10275 Science Center Drive, San Diego, CA 92121, USA. [email protected]
PMID: 14592510 DOI: 10.1016/j.bmcl.2003.08.048
Abstract

New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic increase of exposure compared to our reference compound, 3 (LG101506).