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.
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