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

Abstract

The syntheses of the meso-1,2-dialkyl-1,2-bis(3'-hydroxyphenyl)ethanes [alkyl substituent: CH3 (I) [78682-42-5], C2H5 (II) [71953-72-5], C3H7 (III) [78682-43-6], C4H9 (IV) [78682-44-7], i-C4H9 (V) [78682-45-8], and C5H11 (VI) [78682-46-9]] and of d,l-3,4-bis(3'-hydroxyphenyl)hexane [71953-71-4] are described. In vitro these compds. inhibited the 3H-labeled estradiol [50-28-2] receptor interaction competitively, exhibiting Ka values of 0.20 * 109-0.11 * 106 M-1. In vivo the meso compds. reduced the estrone [53-16-7]-stimulated mouse uterine growth; the most effective compds. were II, III and IV (48, 50, and 45% inhibition, resp.). Compds., II-V showed weak estrogenic activity in the mouse uterine wt. test and in the vaginal cornification test. Compds. I, II, and III exhibited a dose-dependent growth inhibition on the MCF-7 human breast tumor cell line (10-9-10-6 M). These compds. also showed a marked dose-dependent inhibition on the DMBA-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat corresponding to their assocn. consts.