17α-(二甲基苯基)乙烯雌二醇的合成与评价作为雌激素受体-α配体结合域的探针。
Synthesis and evaluation of 17α-(dimethylphenyl)vinyl estradiols as probes of the estrogen receptor-α ligand binding domain.
机构信息
Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, United States.
出版信息
Steroids. 2012 Apr;77(5):471-6. doi: 10.1016/j.steroids.2012.01.003. Epub 2012 Jan 17.
Abstract
As part of our program to explore the influence of small structural modifications on the biological response of the estrogen receptor-α (ERα), we prepared and evaluated a series of mono-and di-substituted phenyl vinyl estradiols. The target compounds were prepared in 45-80% yields using the Stille coupling reaction and evaluated using competitive binding analysis with the ERα-ligand binding domain (hERα-LBD) and estrogenic activity (induction of alkaline phosphatase in Ishikawa cells). Results indicated that the 2,4- and 2,5-dimethyl derivatives, 5b and 5c, had the highest relative binding affinity (RBA=20.5 and 37.3%) and relative stimulatory activity (RSA=101.0% and 12.3%) of the di-methyl series.
摘要
作为我们探索小结构修饰对雌激素受体-α（ERα）生物学反应影响的计划的一部分，我们制备并评估了一系列单取代和二取代苯基乙烯雌酚。使用 Stille 偶联反应以 45-80%的产率制备目标化合物，并使用与 ERα-配体结合域（hERα-LBD）和雌激素活性（诱导 Ishikawa 细胞碱性磷酸酶）的竞争结合分析进行评估。结果表明，2,4-和 2,5-二甲基衍生物 5b 和 5c 具有最高的相对结合亲和力（RBA=20.5 和 37.3%）和二甲基系列的相对刺激活性（RSA=101.0%和 12.3%）。
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