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

Sundén, Henrik; Schäfer, Anja; Scheepstra, Marcel; Leysen, Seppe; Malo, Marcus; Ma, Jian-Nong; Burstein, Ethan S; Ottmann, Christian; Brunsveld, Luc and Olsson, Roger LU (2016) In Journal of Medicinal Chemistry 59(3). p.1232-1238
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.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
59
issue
3
pages
1232 - 1238
publisher
American Chemical Society (ACS)
external identifiers
  • pmid:26820900
  • scopus:84958211770
  • wos:000370212700031
ISSN
1520-4804
DOI
10.1021/acs.jmedchem.5b01702
language
English
LU publication?
yes
id
bd75a065-6735-444a-9bea-aec3e0c83efb (old id 8573089)
date added to LUP
2016-02-16 11:21:35
date last changed
2017-10-01 03:32:59
@article{bd75a065-6735-444a-9bea-aec3e0c83efb,
  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.},
  author       = {Sundén, Henrik and Schäfer, Anja and Scheepstra, Marcel and Leysen, Seppe and Malo, Marcus and Ma, Jian-Nong and Burstein, Ethan S and Ottmann, Christian and Brunsveld, Luc and Olsson, Roger},
  issn         = {1520-4804},
  language     = {eng},
  number       = {3},
  pages        = {1232--1238},
  publisher    = {American Chemical Society (ACS)},
  series       = {Journal of Medicinal Chemistry},
  title        = {Chiral Dihydrobenzofuran Acids Show Potent Retinoid X Receptor-Nuclear Receptor Related 1 Protein Dimer Activation.},
  url          = {http://dx.doi.org/10.1021/acs.jmedchem.5b01702},
  volume       = {59},
  year         = {2016},
}