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Design, Synthesis, and Structure-Activity Analysis of Isoform-Selective Retinoic Acid Receptor Beta Ligands

Birgitte W Lund, Anne Eeg Knapp, Fabrice Piu, Natalie K Gauthier, Mikael Begtrup, Uli Hacksell, Roger Olsson

J Med Chem. 2009 Mar 26;52(6):1540-5.

PMID: 19239230

Abstract:

We recently discovered the isoform selective RAR beta 2 ligand 4'-octyl-4-biphenylcarboxylic acid (3, AC-55649). Although 3 is highly potent at RAR beta 2 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 RAR beta 2.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP59662496 AC-55649 AC-55649 59662-49-6 Price
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