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 (3, AC-55649). Although 3 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 3. This ultimately led to the design of 28, a novel, orally available ligand with excellent isoform selectivity for the RARβ2.