摘要
We have previously found that several families of nonpolar short chain 11β-ethers and esters ofestradiol are selective estrogen receptor modulators （SERMs）. Surprisingly, the transformation from potent estrogen to anti-estrogen occurs when the 11β-side chain is increased slightly in length from four to five non-hydrogen atoms. To generate strong antagonists for preclinical development, we have synthesized other similar ER ligands with 11β-ethers and with an additional ethinyl group at the 17β-position in order to slow metabolism of the steroidal moiety. Here we report the synthesis and biological activity of two such compounds （11β-i-PrO-propyl and 11β-t-BuO-propyl ethers） with extremely strong antagonist activities.
We have previously found that several families of nonpolar short chain 11β-ethers and esters ofestradiol are selective estrogen receptor modulators （SERMs）. Surprisingly, the transformation from potent estrogen to anti-estrogen occurs when the 11β-side chain is increased slightly in length from four to five non-hydrogen atoms. To generate strong antagonists for preclinical development, we have synthesized other similar ER ligands with 11β-ethers and with an additional ethinyl group at the 17β-position in order to slow metabolism of the steroidal moiety. Here we report the synthesis and biological activity of two such compounds （11β-i-PrO-propyl and 11β-t-BuO-propyl ethers） with extremely strong antagonist activities.
