Acetoxy substituted 1,1,2-triphenylbut-1-enes: estrogenic, antiestrogenic and mammary tumor inhibiting activity.
1,1,2-Triphenylbut-1-enes substituted with 3- or 4-acetoxy (OAc) groups on one, two, or three phenyl rings were tested for their estrogen receptor affinities, their estrogenic and antiestrogenic properties in the immature mouse, and their effect on the growth of the hormone-dependent MXT mammary tumor of the mouse. The 4-OAc-substituted compounds had a stronger uterotrophic potency than their 3-OAc-substituted analogs. A certain correlation between estrogenic properties and receptor affinities was demonstrable. Compounds with 3-OAc groups generally had antiestrogenic properties. By varying the aromatic substitution it was possible to obtain compounds ranging from strong estrogens to potent antiestrogens with almost no agonistic activity. The 4-OAc-substituted triphenylbut-1-enes had a better antitumor effect than the compounds with 3-OAc moieties. Thus, the tumor inhibiting activity correlates more with the estrogenic than with the antiestrogenic properties. The strong antiestrogens among these compounds did not show any significant antitumor effect. Further studies are necessary to solve the problem why strong antiestrogens do not, in contrast to ovariectomy, inhibit tumor growth.
D000475:Alkenes / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship
D000475:Alkenes; D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D004967:Estrogens; C035804:1,1,2-triphenylbut-1-ene