ESTROGEN RECEPTOR LIGANDS.PART 15:SYNTHESIS OF BENZOTHIOPYRAN-BASED SELECTIVE ESTROGEN RECEPTOR ALPHA MODULATORS(SERAM)

摘要

Benzothiopyran(2)was prepared and the bioactive(+)-2 was found to exhibit a reduced affinity toward the estrogen receptors(ER alpha/beta)when compared to the corresponding dihydrobenzoxathiin(+)-1.In a previous communication,we identified ERa subtype selective ligands or Selective Estrogen Receptor Alpha Modulators(SERAMs)that centered on the dihydrobenzoxathiin core structure.This compound,as exemplified by 1,exhibited low nanomolar binding affinity and sub-nanomolar functional activity,as well as in vivo efficacy for the suppression of estradiol-driven uterine proliferation,with minimal uterotropic activity.Subsequent expanded structure-activity relationship eventually led to a potential developmental candidate.