Qian X D, Abul-Hajj Y J
Departmnt of Medicinal Chemistry and Pharmacognosy, University of Minnesota, Minneapolis 55455.
J Steroid Biochem. 1988 Jun;29(6):657-63. doi: 10.1016/0022-4731(88)90166-5.
The dialkylaminoethoxy side chain in triphenylethylene antiestrogens is required for their antiestrogenic activity. Without this side chain the compounds lose their antiestrogenic activity and become essentially estrogenic. Estradiol substituted at the 17 beta-position with dialkylaminoethoxy, dialkylaminoethylamino, or dialkylaminoethylthiol were synthesized and tested for their ability to displace estradiol for its receptor. All of the derivatives tested exhibited low binding affinities to the estrogen receptor, with RBA values ranging between 0 to 1.2 (estradiol = 100). The mouse and rat uterine weight test revealed only low estrogenic activity for this class of compounds. None of the estradiol derivatives synthesized showed antiestrogenic activity.
三苯乙烯类抗雌激素药物中的二烷基氨基乙氧基侧链是其抗雌激素活性所必需的。没有这个侧链，这些化合物就会失去抗雌激素活性并基本上变成雌激素样。合成了在17β位被二烷基氨基乙氧基、二烷基氨基乙氨基或二烷基氨基乙硫醇取代的雌二醇，并测试了它们取代雌二醇与受体结合的能力。所有测试的衍生物对雌激素受体的结合亲和力都很低，相对结合活性（RBA）值在0至1.2之间（雌二醇=100）。小鼠和大鼠子宫重量试验表明这类化合物只有低雌激素活性。合成的所有雌二醇衍生物均未显示抗雌激素活性。
