ANTIESTROGENIC AND ANTIFERTILITY PROPERTIES OF SOME BASIC ETHER DERIVATIVES OF DIMETHYLSTILBESTROL AND RELATED COMPOUNDS

¹ Department of Veterinary Physiology, University of Sydney, Sydney, New South Wales, Australia

A number of mono-and bisbasic ether derivatives of trans--methyl- and trans-, dimethylstilbene-4,4'-diol, -methyl-4 ,4'-dihydroxybibenzyl and meso- and dl-, -dimethyl-4 ,4'-dihydroxybibenzyl have been tested for estrogenic and antiestrogenic activity, both intravaginally and s.c., and for antifertility activity by s.c. injection in mice. Almost all of the compounds tested showed antiestrogenic activity in the local assay, but only 4-[2-(N,N-diethylamino) ethoxy]-4'-ydroxy- methylbibenzyl hydrochloride and 4-[ -(N , N-diethylamino) ethoxy]-4'- methoxy-- methylbibenzyl citrate were active s.c. Neither of these showed antifertility activity. None of the trans-, -dimethylstilbene-4,4'-diol (dimethylstilbestrol) derivatives showed antifertility activity. Six basic ether derivatives of meso- , -dimethyl-4,4'-dihydroxybibenzyl showed antifertility activity at doses corresponding to the estrogenic ED50, except in the case of erythro-4-[2-(N, N-diethylamino)ethoxy]-, -dimethyl-4'-hydroxybibenzyl, which had an antifertility ED50 of 200 µg, one-fifth of its estrogenic ED50. Structure-activity relationships of the compounds examined are discussed and compared with those reported for basic ether derivatives of triarylethylenes, -ethanes and other analogous compounds.