Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
J Med Chem. 2004 Nov 18;47(24):5872-93.

Pyrazolo[1,5-a]pyrimidines: estrogen receptor ligands possessing estrogen receptor beta antagonist activity.

Author information

  • 1Department of Chemistry and Department of Molecular and Integrative Physiology, University of Illinois, 600 South Matthews Avenue, Urbana, Illinois 61801, USA.

Erratum in

  • J Med Chem. 2005 Apr 7;48(7):2724.


In our search for novel subtype-selective estrogen receptor (ER) ligands, we have examined various heterocyclic units as core structural elements. Here, we have investigated the fused, bicyclic pyrazolo[1,5-a]pyrimidine core, which is a system that allows for analogues to be readily assembled in a library-like fashion. This series of pyrazolo[1,5-a]pyrimidine ER ligands provided us with a new pharmacological profile for an ER ligand: compounds that are passive on both ERs, with a distinct potency selectivity in favor of ERbeta. The most distinctive ligand in this series, 2-phenyl-3-(4-hydroxyphenyl)-5,7-bis(trifluoromethyl)-pyrazolo[1,5-a]pyrimidine, was 36-fold selective for ERbeta in binding. Curiously, on the basis of molecular modeling, the ERbeta binding selectivity of compounds in this series appears to be derived from differing orientations that they adapt in the ligand binding pockets of ERalpha vs ERbeta. In transcription assays this pyrazolopyrimidine was fully effective as an ERbeta antagonist while exhibiting no significant activity on ERalpha. Thus, this ligand functions as a potency- and efficacy-selective ERbeta antagonist that would abrogate estrogen action through ERbeta with minimal effects on its activity through ERalpha; as such, it could be used to study the biological function of ERbeta.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Icon for American Chemical Society
    Loading ...
    Write to the Help Desk