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Chiral Dihydrobenzofuran Acids Show Potent Retinoid X Receptor-Nuclear Receptor Related 1 Protein Dimer Activation.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Sundén H,Schäfer A,Scheepstra M,Leysen S,Malo M,Ma JN,Burstein ES,Ottmann C,Brunsveld L,Olsson R

doi

10.1021/acs.jmedchem.5b01702

subject

Has Abstract

pub_date

2016-02-11 00:00:00

pages

1232-8

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

59

pub_type

杂志文章

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