Analogues of [(triethylsilyl)ethynyl]estradiol as potential antifertility agents

Article abstract of DOI:10.1021/jm00398a014

Various 17α-ethynylsteroids were prepared and derivatized as the corresponding triethylsilyl compounds 2-35, which were examined for a ratio of antifertility to estrogenic activity that would be more beneficial than that of the presently used agent. Among the triethylsilyl compounds evaluated, only 23 displayed this desired ratio, although two other compounds without the triethylsilyl moiety, 18 and 26, shared similar characteristics. In a previous study of ethynyl estradiol derivatives by the authors, it was found that even a small presence of silicon was beneficial. The silyl derivatives showed a reduction in estrogenic activity along with a retention of the level of oral antifertility activity. In relation to endocrine disorders and the undesired side effects of prescribed contraceptives, the finding is positive. In the present study, the effects of structural changes in the A, B, C, and D rings of the ethynyl estradiol steroidal nucleus were examined in conjunction with C-21 triethylsilyl moiety. The general method of Ethynylation and Triethylsilylation are described in detail and the oral antifertility and oral estrogenic potencies of the compounds are described and compared. Of the various triethylsilyl compounds examined for an antifertility to estrogenic activity ration that would be more beneficial than that of a present agent, only 23 manifested the desired ratio. Compound 18, which was 66% as effective as ethynyl estradiol as an antifertility agent, had 0.1% of the estrogenic activity of ethynyl estradiol and was singled out for the greatest separation between antifertility activity and estrogenic activity. 2 groups of rats, 1 immature females and the other adult, female, cycling rats were tested for oral estrogenic activity and oral antifertility activity, respectively.