Hanson R N, Napolitano E, Fiaschi R
Department of Pharmaceutical Sciences, Bouve College of Pharmacy and Health Sciences, Northeastern University, Boston, Massachusetts, USA.
Steroids. 1998 Sep;63(9):479-83. doi: 10.1016/s0039-128x(98)00052-x.
Previous studies from our laboratory demonstrated separately the tolerance of the estrogen receptor for the 17 alpha-phenylselenovinyl substituent and the enhancement of affinity imparted by the 11 beta-vinyl moiety. Our recent publication suggested that the two groups could be combined within a single structure and retain high affinity for the estrogen receptor. As a result, we have prepared in good overall yields the E- and Z-isomers of 11 beta-vinyl-17 alpha-phenylselenovinyl estradiol. Evaluation of the new steroids with receptor isolated from lamb cytosol indicated that both isomers are poorer ligands than estradiol at 4 degrees C, but both are better than estradiols. at 25 degrees C. This behavior had not been observed for the 11 beta-unsubstituted 17 alpha-E/Z phenylselenovinyl estradiols. Of particular interest was the observation that, unlike previous isomer pairs, the E-isomer possessed a greater affinity than the Z-isomer. The results suggest that relatively small changes in structure may impart significant differences in the interactions with the receptor and provide the basis for further ligand design.
我们实验室之前的研究分别证明了雌激素受体对17α-苯硒基乙烯基取代基的耐受性以及11β-乙烯基部分赋予的亲和力增强。我们最近的出版物表明，这两个基团可以结合在一个单一结构中，并对雌激素受体保持高亲和力。因此，我们以良好的总收率制备了11β-乙烯基-17α-苯硒基乙烯基雌二醇的E型和Z型异构体。用从羊细胞质中分离出的受体对新的甾体进行评估表明，在4℃时，两种异构体都是比雌二醇更差的配体，但在25℃时，两者都比雌二醇好。对于11β-未取代的17α-E/Z苯硒基乙烯基雌二醇，尚未观察到这种行为。特别有趣的是观察到，与之前的异构体对不同，E型异构体比Z型异构体具有更高的亲和力。结果表明，结构上相对较小的变化可能会在与受体的相互作用中产生显著差异，并为进一步的配体设计提供基础。
