Chiral dihydrobenzofuran acids show potent retinoid X receptor-nuclear receptor related 1 protein dimer activation

H. Sundén, A. Schäfer, M. Scheepstra, S. Leysen, M. Malo, Jian-Nong Ma, E.S. Burstein, Chr. Ottmann, L. Brunsveld, R. Olsson

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
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Abstract

The nuclear receptor Nurr1 can be activated by RXR via heterodimerization (RXR-Nurr1) and is a promising target for treating neurodegenerative diseases. We herein report the enantioselective synthesis and SAR of sterically constricted benzofurans at RXR. The established SAR, using whole cell functional assays, lead to the full agonist 9a at RXR (pEC50 of 8.2) and RXR-Nurr1. The X-ray structure shows enantiomeric discrimination where 9a optimally addresses the ligand binding pocket of RXR.

Original languageEnglish
Pages (from-to)1232-1238
Number of pages7
JournalJournal of Medicinal Chemistry
Volume59
Issue number3
DOIs
Publication statusPublished - 11 Feb 2016

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