Potential antiestrogens. Synthesis and evaluation of mammary tumor inhibiting activity of 1,2-dialkyl-1,2-bis(3'-hydroxyphenyl)ethanes

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Abstract
The syntheses of the meso-1,2-dialkyl-1,2-bis(3''-hydroxyphenyl)ethanes [alkyl substituent: CH3 (19), C2H5 (20), C3H7 (22), C4H9 (23), i-C4H9 (24), and C5H11 (25)] and of d,l-3,4-gis(3''-hydroxpyphenyl)hexane (21) are described. In vitro these compounds inhibited the [3H]estradiol receptor interaction competitively, exhibiting Ka values between 0.20 .times. 109 (20) and 0.11 .times. 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 45% 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 [9,10-dimethyl-1,2-benzanthracene] induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat corresponding to their association constants.