Synthesis of 11β-ether-17α-ethinyl-3,17β-estradiols with strong ER antagonist activities  

作　　者：Jing-Xin Zhang David C.Labaree Richard B.Hochberg 

机构地区：[1]Department of Obstetrics,Gynecology & Reproductive Sciences,Yale University School of Medicine

出　　处：《Chinese Chemical Letters》2014年第4期567-570,共4页中国化学快报（英文版）

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.

关 键 词：Estrogen receptor SERM Antagonist Estradiol 

分 类 号：TQ460.1[化学工程—制药化工]