Design of a Highly Selective and Potent Class of Non-planar Estrogen Receptor Agonists
Journal article, 2013
Selective activation of the estrogen receptor (ER) could be a safe approach to hormone replacement therapy for both women and men, in contrast to the estrogens currently used for women which activate both ER and ER, occasionally causing severe side effects. cis-10-SR, was shown to have an EC50 value of <1nM, potency 100-fold higher than that of AC-131. Even more interestingly, compound trans-10-SS exhibited 1000-fold ER/ER selectivity while still maintaining good potency (approximate to 10nM). In addition, trans-10-SS showed only partial agonist activity (30-60% Eff.) toward ER at 10M. trans-10-SS appears to be the first molecule to take advantage of both conservative amino acid differences found in the - and -faces of the binding cavities of ER and ER beta.
enantioselective synthesis
Parkinson's disease
estrogen receptors
antipsychotics
asymmetric synthesis
(-)-galanthamine
endogenous sex-hormones
modulation
beta-agonist
neurological agents
modulators
inflammation
identification
alpha-iodination
inverse agonists
Author
Henrik Sundén
University of Gothenburg
J. N. Ma
L. K. Hansen
A. L. Gustavsson
E. S. Burstein
Roger Olsson
University of Gothenburg
ChemMedChem
1860-7179 (ISSN) 1860-7187 (eISSN)
Vol. 8 8 1283-1294Subject Categories
Chemical Sciences
DOI
10.1002/cmdc.201300175