Chiral Dihydrobenzofuran Acids Show Potent Retinoid X Receptor-Nuclear Receptor Related 1 Protein Dimer Activation.
(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.
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8573089
- author
- Sundén, Henrik ; Schäfer, Anja ; Scheepstra, Marcel ; Leysen, Seppe ; Malo, Marcus ; Ma, Jian-Nong ; Burstein, Ethan S ; Ottmann, Christian ; Brunsveld, Luc and Olsson, Roger LU
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Medicinal Chemistry
- volume
- 59
- issue
- 3
- pages
- 1232 - 1238
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:26820900
- scopus:84958211770
- wos:000370212700031
- pmid:26820900
- 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
- 2016-04-01 11:13:58
- date last changed
- 2022-04-05 01:07:10
@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 = {{The 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}}, doi = {{10.1021/acs.jmedchem.5b01702}}, volume = {{59}}, year = {{2016}}, }