Cytotoxic estrogens: anilin mustard linked 1,1,2-triphenylbut-1-enes with mammary tumor inhibiting activity.

In order to develop cytotoxic estrogens with a specific effect on hormone-dependent mammary tumors, two 1,1,2-triphenylbut-1-enes with a 4-OH group at one C-1-phenyl ring and a chloro-[4] or bromo-[8] anilin mustard moiety at the other C-1-phenyl ring were synthesized. 4 and 8 exerted strong alkylating activity and an irreversible binding to the estrogen receptor. In spite of relatively low receptor affinities, both anilin mustards exhibited a better effect on a receptor-positive breast cancer cell line as well as on a hormone-dependent mammary carcinoma of the mouse than on a receptor-negative cell line and a hormone-independent mammary carcinoma. Therefore, a selective antitumor activity of 4 and 8 is likely.