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.