Antiestrogens. Synthesis and evaluation of mammary tumor inhibiting activity of 1,1,2,2-tetraalkyl-1,2-diphenylethanes

Abstract

Among the newly synthesized 1,1,2,2-tetraalkyl-1,2-diphenylethanes, 1,1,2,2-tetramethyl-1,2-bis(4''-hydroxyphenyl)ethane (23) and 1,1,2,2-tetramethyl-1,2-bis(3''-hydroxyphenyl)ethane (26) were the most active compounds regarding estradiol receptor affinity, exhibiting Ka values of 0.73 .times. 108 and 0.67 .times. 108 M-1, respectively. In vivo, 23 and 26 showed only very small uterotrophic activity in the mouse. They strongly inhibited (73%) the estrone-stimulated mouse uterine growth. Tested on the 9,10-dimethyl-1,2-benzanthracene induced hormone-dependent mammary adenocarcinoma of the Sprague-Dawley rat, compounds 23 and 26 exhibited a dose-dependent inhibition of the tumor growth, having a strong effect at a dose of 20 (mg/kg) per day (compound 23).