10.1021/jm801532e.s002 Birgitte W. Lund Birgitte W. Lund Anne Eeg Knapp Anne Eeg Knapp Fabrice Piu Fabrice Piu Natalie K. Gauthier Natalie K. Gauthier Mikael Begtrup Mikael Begtrup Uli Hacksell Uli Hacksell Roger Olsson Roger Olsson Design, Synthesis, and Structure−Activity Analysis of Isoform-Selective Retinoic Acid Receptor β Ligands American Chemical Society 2009 solubility issues phenylthiazole series Receptor β LigandsWe AC RAR β2 SAR isoform selectivity ligand drug development 2009-03-26 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Design_Synthesis_and_Structure_Activity_Analysis_of_Isoform_Selective_Retinoic_Acid_Receptor_Ligands/2868631 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.