2Q70

Estrogen receptor alpha ligand-binding domain complxed to a benzopyran ligand

Summary for 2Q70

• Entry DOI: 10.2210/pdb2q70/pdb
• Related: 2I0J 2POG
• Descriptor: Estrogen receptor, (3AS,4R,9BR)-2,2-DIFLUORO-4-(4-HYDROXYPHENYL)-1,2,3,3A,4,9B-HEXAHYDROCYCLOPENTA[C]CHROMEN-8-OL (3 entities in total)
• Functional Keywords: transcription factor, estrogen receptor, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Nucleus. Isoform 3: Nucleus: P03372
• Total number of polymer chains: 2
• Total formula weight: 57230.97

Authors

Wang, Y. (deposition date: 2007-06-05, release date: 2007-08-07, Last modification date: 2024-02-21)

Primary citation

Richardson, T.I.,Dodge, J.A.,Durst, G.L.,Pfeifer, L.A.,Shah, J.,Wang, Y.,Durbin, J.D.,Krishnan, V.,Norman, B.H.
Benzopyrans as selective estrogen receptor beta agonists (SERBAs). Part 3: synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification.
Bioorg.Med.Chem.Lett., 17:4824-4828, 2007

PubMed Abstract: Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the syntheses of cyclopentanone and cyclohexanone intermediates for SAR studies of the C-ring on the benzopyran scaffold. Modification of the C-ring disrupts binding to ERalpha, thus improving ERbeta selectivity up to 100-fold. X-ray cocrystal structures confirm previously observed binding modes.

PubMed: 17614275
DOI: 10.1016/j.bmcl.2007.06.052

Experimental method

X-RAY DIFFRACTION (1.95 Å)