Schneider M R, Schönenberger H, Michel R T, Fortmeyer H P
J Med Chem. 1982 Feb;25(2):141-5. doi: 10.1021/jm00344a010.
3,3'-Diacetoxy-alpha, beta-dialkylstilbenes (alkyl = CH3 to C4H9, 1-4) 3,3'-dihydroxy-alpha, beta-diethylstilbene (5), and their corresponding stilbene oxides (6-10) were synthesized. Compounds 1-10 competitively antagonized in vitro the interaction of [3H]estradiol with its receptor. 3,3'-Diacetoxy-alpha, beta-diethylstilbene (2), 3,3'-diacetoxy-alpha, beta-diethylstilbene oxide (7), and their phenolic analogues (5 and 10) were most effective. Shortening or lengthening the alkyl side chains led to a decrease in receptor affinity. Among the stilbenes and epoxides, those with C2H5 and C3H7 groups (2, 3, 5 and 7, 8, 10) caused the strongest inhibition of the growth of a hormone-dependent postmenopausal human mammary carcinoma serially implanted in nude mice. The strong antitumor activity of 5 and 10 was confirmed by experiments on the 9,10-dimethyl-1,2-benzanthracene-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat.
合成了3,3'-二乙酰氧基-α,β-二烷基芪（烷基 = CH3至C4H9，1 - 4）、3,3'-二羟基-α,β-二乙基芪（5）及其相应的芪氧化物（6 - 10）。化合物1 - 10在体外竞争性拮抗[3H]雌二醇与其受体的相互作用。3,3'-二乙酰氧基-α,β-二乙基芪（2）、3,3'-二乙酰氧基-α,β-二乙基芪氧化物（7）及其酚类类似物（5和10）最为有效。缩短或延长烷基侧链会导致受体亲和力降低。在芪类和环氧化合物中，含有C2H5和C3H7基团的化合物（2、3、5以及7、8、10）对连续接种于裸鼠的激素依赖性绝经后人类乳腺癌生长的抑制作用最强。5和10的强抗肿瘤活性在对9,10 - 二甲基 - 1,2 - 苯并蒽诱导的斯普拉格 - 道利大鼠激素依赖性乳腺癌的实验中得到证实。
