Hanson Robert N, Friel Carolyn J, Dilis Robert, Hughes Alun, DeSombre Eugene R
Department of Chemistry, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115-5000, USA.
J Med Chem. 2005 Jun 30;48(13):4300-11. doi: 10.1021/jm040157s.
As part of our ongoing program to develop probes for the hormone binding domain of the estrogen receptor-alpha (ERalpha), we prepared and evaluated a series of 17alpha,Z-(4-substituted-phenyl)vinyl estradiol derivatives. The results indicated that the relative binding affinities (RBAs) at 25 degrees C for the new compounds were significant (RBA = 9-57) although less than that of estradiol (RBA = 100) or of the parent unsubstituted phenylvinyl estradiol (RBA = 66). All of the Z-compounds were full agonists in the uterotrophic assay, indicating that the ligands formed estrogen-like complexes with the estrogen receptor-alpha hormone binding domain (ERalpha-HBD). Comparison of corresponding Z- and E-4-substituted phenylvinyl ligands complexed with the ERalpha-HBD indicated small but significant differences in binding modes that may account for the differing trends seen in the structure-activity relationships for the two series.
作为我们开发雌激素受体α（ERα）激素结合域探针的持续项目的一部分，我们制备并评估了一系列17α，Z-（4-取代苯基）乙烯基雌二醇衍生物。结果表明，新化合物在25℃下的相对结合亲和力（RBA）显著（RBA = 9 - 57），尽管低于雌二醇（RBA = 100）或未取代的母体苯基乙烯基雌二醇（RBA = 66）。所有Z-化合物在子宫增重试验中都是完全激动剂，表明这些配体与雌激素受体α激素结合域（ERα-HBD）形成了类似雌激素的复合物。与ERα-HBD复合的相应Z-和E-4-取代苯基乙烯基配体的比较表明，结合模式存在微小但显著的差异，这可能解释了两个系列在构效关系中出现的不同趋势。
