Peters R H, Crowe D F, Tanabe M, Avery M A, Chong W K
J Med Chem. 1987 Apr;30(4):646-52. doi: 10.1021/jm00387a011.
A number of silicon-substituted analogues of ethynylestradiol that exhibit modified and enhanced biological activities have been synthesized. Particularly noteworthy are a group of [(trialkylsilyl)ethynyl]estradiol analogues that exhibit high antifertility potency and markedly reduced estrogenic activity. The best compounds synthesized are 17 alpha-[(triethylsilyl)ethynyl]estradiol (5) and 17 alpha-[(tert-butyldimethylsilyl)ethynyl]estradiol (33), which show a separation of antifertility from estrogenic activity in the rat. The results of structure-activity studies indicate a good correlation between the observed biological activities and the calculated van der Waals volumes of the three variable silicon substituents.
已经合成了许多具有修饰和增强生物活性的乙炔雌二醇的硅取代类似物。特别值得注意的是一组[(三烷基甲硅烷基)乙炔基]雌二醇类似物，它们表现出高抗生育效力且雌激素活性显著降低。所合成的最佳化合物是17α-[(三乙基甲硅烷基)乙炔基]雌二醇(5)和17α-[(叔丁基二甲基甲硅烷基)乙炔基]雌二醇(33)，它们在大鼠中显示出抗生育活性与雌激素活性的分离。构效关系研究结果表明，观察到的生物活性与三个可变硅取代基的计算范德华体积之间具有良好的相关性。
