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

• DOI: 10.1016/j.bmcl.2003.08.048
• Publication Date: 2003-10-15T11:38:36Z
• Authors: Pierre-Yves Miche...; 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
• Keywords: Male; 0303 health sciences; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Tretinoin; Retinoic Acid Receptor gamma; Binding, Competitive; Cell Line; 3. Good health; Kinetics; Mice; 03 medical and health sciences; Retinoid X Receptors; Coumarins; Drug Design; Animals; Transcription Factors

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).