Design of a Highly Selective and Potent Class of Non-planar Estrogen Receptor Agonists
Artikel i vetenskaplig tidskrift, 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

Författare

Henrik Sundén

Göteborgs universitet

J. N. Ma

L. K. Hansen

A. L. Gustavsson

E. S. Burstein

Roger Olsson

Göteborgs universitet

ChemMedChem

1860-7179 (ISSN) 1860-7187 (eISSN)

Vol. 8 1283-1294

Ämneskategorier

Kemi

DOI

10.1002/cmdc.201300175