Schneider M R, Ball H, Schiller C D
J Med Chem. 1986 Aug;29(8):1355-62. doi: 10.1021/jm00158a006.
1,1,2-Triphenylbut-1-enes (26-35), which are substituted with one or two 3,4-diacetoxy groups or with one 3,4-diacetoxy and one 3- or 4-acetoxy group in two aromatic rings, were synthesized. The occurring E and Z isomers were isolated, and their identity was established by 1H NMR spectroscopy. A study on structure-activity relationship was carried out with regard to estradiol receptor affinity in vitro, estrogenic and antiestrogenic properties in the immature mouse, and inhibition of the hormone-dependent MXT mammary tumor of the mouse in vivo. Among the tested compounds, most of the 1,1-disubstituted 1,1,2-triphenylbut-1-enes (29, Z-30, Z,E-31) and (E)-1-(3-acetoxyphenyl)-1-phenyl-2-(3,4-diacetoxyphenyl)but- 1-ene (E-35) as well as its respective Z isomer (Z-35) exerted antiestrogenic properties. Compounds Z-30, Z,E-31, Z-35, and E-35 inhibited the growth of the hormone-dependent MXT tumor. The best antitumor effect without estrogenic side effects during therapy was shown by E-35.
合成了1,1,2-三苯基丁-1-烯（26 - 35），其在两个芳香环中被一个或两个3,4 - 二乙酰氧基或一个3,4 - 二乙酰氧基和一个3 - 或4 - 乙酰氧基取代。分离出了出现的E型和Z型异构体，并通过1H NMR光谱确定了它们的结构。针对体外雌二醇受体亲和力、未成熟小鼠的雌激素和抗雌激素特性以及体内对小鼠激素依赖性MXT乳腺肿瘤的抑制作用，开展了构效关系研究。在测试的化合物中，大多数1,1 - 二取代的1,1,2 - 三苯基丁-1-烯（29、Z - 30、Z,E - 31）以及（E）-1-（3 - 乙酰氧基苯基）-1 - 苯基-2-（3,4 - 二乙酰氧基苯基）丁-1-烯（E - 35）及其相应的Z型异构体（Z - 35）具有抗雌激素特性。化合物Z - 30、Z,E - 31、Z - 35和E - 35抑制了激素依赖性MXT肿瘤的生长。E - 35在治疗期间表现出最佳的抗肿瘤效果且无雌激素副作用。
