Design, synthesis, and structure-activity analysis of isoform-selective retinoic acid receptor ß ligands

Research output: Contribution to journalJournal articleResearchpeer-review

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

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.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume52
Issue number6
Pages (from-to)1540-1545
ISSN0022-2623
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: Cell Line, Tumor; Drug Design; Humans; Ligands; Receptors, Retinoic Acid; Structure-Activity Relationship

ID: 18652140