Antiestrogens. Synthesis and evaluation of mammary tumor inhibiting activity of 1,1,2,2-tetraalkyl-1,2 -diphenylethanes.
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 X 10(8) and 0.67 X 10(8) 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)/day (compound 23).
D000818:Animals; D002417:Cattle; D004958:Estradiol / Q000378:metabolism; D045166:Estradiol Congeners / Q000138:chemical synthesis; D004965:Estrogen Antagonists / Q000138:chemical synthesis* / Q000627:therapeutic use; D004980:Ethane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D045166:Estradiol Congeners; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D004958:Estradiol; D004980:Ethane