Potential Antiestrogens. Synthesis and Evaluation of Mammary Tumor Inhibiting Activity of 1,2-Dialkyl-1,2-bis(3'-hydroxyphenyl)ethanes

Article abstract of DOI:10.1021/jm00142a014

The syntheses of the meso-1,2-dialkyl-1,2-bis(3'-hydroxyphenyl)ethanes and of d,l-3,4-bis(3'-hydroxyphenyl)hexane (21) are described.In vitro these compounds inhibited the <3H>estradiol receptor interaction competitively, exhibiting K_a values between 0.20*10⁹ (20) and 0.11*10⁶ M^-1 (24).In vivo the meso compounds reduced the estrone-stimulated mouse uterine growth; the most effective compounds were 20, 22, and 23 (53, 50, and 45percent inhibition, respectively).Compounds 20 and 22-24 showed weak estrogenic activity in the mouse uterine weight test and in the vaginal cornification test.Compounds 19 (NSC-297169), 20 (NSC-297170), and 22 (NSC-297171) exhibited a dose-dependent growth inhibition on the MCF-7 human breast tumor cell line (10^-6 to 10^-9 M).These compounds also showed a marked dose-dependent inhibition on the DMBA-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat corresponding to their association constants.