Schneider M R, Schuderer M L
Arch Pharm (Weinheim). 1989 Jan;322(1):59-62. doi: 10.1002/ardp.19893220114.
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.
为了开发对激素依赖性乳腺肿瘤具有特定作用的细胞毒性雌激素，合成了两种1,1,2-三苯基丁-1-烯，其中一个C-1-苯环上有一个4-OH基团，另一个C-1-苯环上有一个氯-[4]或溴-[8]苯胺氮芥部分。4和8表现出很强的烷基化活性以及与雌激素受体的不可逆结合。尽管受体亲和力相对较低，但两种苯胺氮芥对受体阳性乳腺癌细胞系以及对小鼠激素依赖性乳腺癌的作用比对受体阴性细胞系和激素非依赖性乳腺癌的作用更好。因此，4和8可能具有选择性抗肿瘤活性。
