Design of a Highly Selective and Potent Class of Non-planar Estrogen Receptorβ Agonists

• 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.

Subject headings

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Keyword

asymmetric synthesis

neurological agents

estrogen receptors

modulators

Parkinson's disease

endogenous sex-hormones

enantioselective synthesis

alpha-iodination

inverse agonists

beta-agonist

(-)-galanthamine

antipsychotics

identification

inflammation

modulation

enantioselective synthesis

Publication and Content Type

ref (subject category)

art (subject category)