Design, Synthesis, and Structure−Activity Analysis of Isoform-Selective Retinoic Acid Receptor β Ligands
2009-03-26T00:00:00Z (GMT) by
We recently discovered the isoform selective RARβ2 ligand 4′-octyl-4-biphenylcarboxylic acid (<b>3</b>, AC-55649). Although <b>3</b> is highly potent at RARβ2 and displays excellent selectivity, solubility issues make it unsuitable for drug development. Herein we describe the exploration of the SAR in a biphenyl and a phenylthiazole series of analogues of <b>3</b>. This ultimately led to the design of <b>28</b>, a novel, orally available ligand with excellent isoform selectivity for the RARβ2.