3-{4-[4-((7α,17β)-3,17-dihydroxyestra-1,3,5(10)-trien-7-yl)-butyl]-1,2,3-triazol-1-yl}-7-hydroxy-1-benzopyran-2-one | 1428627-96-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3-{4-[4-((7α,17β)-3,17-dihydroxyestra-1,3,5(10)-trien-7-yl)-butyl]-1,2,3-triazol-1-yl}-7-hydroxy-1-benzopyran-2-one
• 英文别名: 3-[4-[4-[(7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-7-yl]butyl]triazol-1-yl]-7-hydroxychromen-2-one
• CAS: 1428627-96-6
• 化学式: C₃₃H₃₇N₃O₅
• 分子量: 555.674
• InChiKey: YPLWXUBAJNIFDO-UGVMDCGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  雌二醇 在 盐酸 、 三乙基硅烷 、 sodium azide 、 copper(ll) sulfate pentahydrate 、 三氟化硼乙醚 、 potassium tert-butylate 、 双氧水 、 4-甲基苯磺酸吡啶 、 sodium ascorbate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 74.67h， 生成 3-{4-[4-((7α,17β)-3,17-dihydroxyestra-1,3,5(10)-trien-7-yl)-butyl]-1,2,3-triazol-1-yl}-7-hydroxy-1-benzopyran-2-one
  参考文献：
  名称：

  Synthesis of Novel Estrogen Receptor Antagonists Using Metal-Catalyzed Coupling Reactions and Characterization of Their Biological Activity

  摘要：

  Estrogen receptor (ER) antagonists are valuable in the treatment of ER-positive human breast cancer. In this study, we designed and synthesized nine new derivatives of 17 beta-estradiol (E-2) with a bulky side chain attached to its C-7 alpha position, and determined their ER antagonistic activity using in vitro bioassays. Four of the derivatives showed a strong inhibition of ER alpha transactivation activity in a luciferase reporter assay and blocked ER alpha interactions with coactivators. Similarly, these derivatives also strongly inhibited the growth of the ER alpha-positive human breast cancer cells. Computational docking analysis was conducted to model the interaction of these antagonists with the human ER alpha and showed that they could tightly bind to the ER alpha in a manner similar to that of ICI-182,780, a pure ER antagonist. These results provide an example that attachment of a bulky side chain to the C-7 alpha position of E-2 can produce ER antagonists with ER affinity comparable to that of ICI-182, 780.

  DOI：

  10.1021/jm3013773

文献信息

• Synthesis of Novel Estrogen Receptor Antagonists Using Metal-Catalyzed Coupling Reactions and Characterization of Their Biological Activity
  作者：Xiang-Rong Jiang、Pan Wang、Carolyn L. Smith、Bao Ting Zhu

  DOI：10.1021/jm3013773

  日期：2013.4.11

  Estrogen receptor (ER) antagonists are valuable in the treatment of ER-positive human breast cancer. In this study, we designed and synthesized nine new derivatives of 17 beta-estradiol (E-2) with a bulky side chain attached to its C-7 alpha position, and determined their ER antagonistic activity using in vitro bioassays. Four of the derivatives showed a strong inhibition of ER alpha transactivation activity in a luciferase reporter assay and blocked ER alpha interactions with coactivators. Similarly, these derivatives also strongly inhibited the growth of the ER alpha-positive human breast cancer cells. Computational docking analysis was conducted to model the interaction of these antagonists with the human ER alpha and showed that they could tightly bind to the ER alpha in a manner similar to that of ICI-182,780, a pure ER antagonist. These results provide an example that attachment of a bulky side chain to the C-7 alpha position of E-2 can produce ER antagonists with ER affinity comparable to that of ICI-182, 780.