9-(4-ethoxyphenyl)-8-phenyl-6,7-dihydro-5H-benzocycloheptene-3-ol | 1610422-66-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 9-(4-ethoxyphenyl)-8-phenyl-6,7-dihydro-5H-benzocycloheptene-3-ol
• 英文别名: 5-(4-ethoxyphenyl)-6-phenyl-8,9-dihydro-7H-benzo[7]annulen-2-ol
• CAS: 1610422-66-6
• 化学式: C₂₅H₂₄O₂
• 分子量: 356.464
• InChiKey: KJTZITGZMHOKOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-甲氧基苯并环庚-5-酮 在 aluminum (III) chloride 、 sodium ethanolate 、 四丁基硫酸氢铵 、 magnesium 、 pyridinium hydrobromide perbromide 、 1,2-二溴乙烷 、 sodium hydroxide 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 二丁醚 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 15.25h， 生成 9-(4-ethoxyphenyl)-8-phenyl-6,7-dihydro-5H-benzocycloheptene-3-ol
  参考文献：
  名称：

  Influence of the Length and Positioning of the Antiestrogenic Side Chain of Endoxifen and 4-Hydroxytamoxifen on Gene Activation and Growth of Estrogen Receptor Positive Cancer Cells

  摘要：

  Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains. Pharmacologic properties were documented in the MCF-7 cell line, and prolactin synthesis was assessed in GH3 rat pituitary tumor cells. The FR Z-isomers of 4OHT and endoxifen were equivalent to 4OHT and endoxifen. Other test compounds used possessed partial estrogenic activity. The E-isomers of FR 4OHT and endoxifen had no estrogenic activity at therapeutic serum concentrations. None of the newly synthesized compounds were able to down-regulate ER levels. Molecular modeling demonstrated that some compounds would each create a best fit with a novel agonist conformation of the ER The results demonstrate modulation by the ER complex of cell replication or gene transcription in cancer.

  DOI：

  10.1021/jm500569h

文献信息

• Influence of the Length and Positioning of the Antiestrogenic Side Chain of Endoxifen and 4-Hydroxytamoxifen on Gene Activation and Growth of Estrogen Receptor Positive Cancer Cells
  作者：Philipp Y. Maximov、Daphne J. Fernandes、Russell E. McDaniel、Cynthia B. Myers、Ramona F. Curpan、V. Craig Jordan

  DOI：10.1021/jm500569h

  日期：2014.6.12

  Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains. Pharmacologic properties were documented in the MCF-7 cell line, and prolactin synthesis was assessed in GH3 rat pituitary tumor cells. The FR Z-isomers of 4OHT and endoxifen were equivalent to 4OHT and endoxifen. Other test compounds used possessed partial estrogenic activity. The E-isomers of FR 4OHT and endoxifen had no estrogenic activity at therapeutic serum concentrations. None of the newly synthesized compounds were able to down-regulate ER levels. Molecular modeling demonstrated that some compounds would each create a best fit with a novel agonist conformation of the ER The results demonstrate modulation by the ER complex of cell replication or gene transcription in cancer.