Synthesis of Estrogen Receptor Beta Selective 17-Substituted Estradiols for the Treatment of Prostate Cancer

摘要

Recent evidence of the presence of ER alpha and ER beta messages in prostatic tissues has appeared recently. Evidence suggested that Estrogen Receptor beta (ER beta) is down regulated during the precancerous prostate intraepithelium neoplasia (PIN) and reappear during the metastatic PC alpha. The applicant has proposed to synthesized novel selective ER beta agonist based on the lead structure l7betaEstradiol, the Estrogen Receptor endogeneous ligand. The applicant has successfully synthesized the first generation of compounds with various aromatic moieties next to the l7alpha-vinyl of estradiol. lH NMR studies show promising results that different aromatic moieties have different electronics influence on the vinyl proton signals which could suggest the selectivity toward ER alpha or ER beta. These results will be confirmed by biological assay which is in progress.