Chiral Dihydrobenzofuran Acids Show Potent Retinoid X Receptor-Nuclear Receptor Related 1 Protein Dimer Activation.
Artikel i vetenskaplig tidskrift, 2016

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.

Författare

Henrik Sundén

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Organisk kemi

Göteborgs universitet

Anja Schäfer

Göteborgs universitet

Marcel Scheepstra

Technische Universiteit Eindhoven

Seppe Leysen

Technische Universiteit Eindhoven

Marcus Malo

Göteborgs universitet

Jian-Nong Ma

ACADIA Pharmaceuticals Inc.

Ethan S Burstein

ACADIA Pharmaceuticals Inc.

Christian Ottmann

Technische Universiteit Eindhoven

Luc Brunsveld

Technische Universiteit Eindhoven

Roger Olsson

Göteborgs universitet

Journal of Medicinal Chemistry

0022-2623 (ISSN) 1520-4804 (eISSN)

Vol. 59 3 1232-1238

Fundament

Grundläggande vetenskaper

Ämneskategorier

Organisk kemi

DOI

10.1021/acs.jmedchem.5b01702

PubMed

26820900

Mer information

Senast uppdaterat

2018-03-20