3-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenoxy)-6,7-dihydro-8-bromo-9-(4-ethoxyphenyl)-5H-benzocycloheptene | 1610422-60-0

• 分子结构分类: 有机化合物
• 英文名称: 3-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenoxy)-6,7-dihydro-8-bromo-9-(4-ethoxyphenyl)-5H-benzocycloheptene
• CAS: 1610422-60-0
• 化学式: C₂₆H₁₈BrF₇O₂
• 分子量: 575.321
• InChiKey: DVJSLNFNVNIYJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.94
• 重原子数：
  36.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  18.46
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenoxy)-6,7-dihydro-8-bromo-9-(4-ethoxyphenyl)-5H-benzocycloheptene 在 sodium ethanolate 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 二丁醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.25h， 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
• 作为产物：
  描述：

  3-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenoxy)-6,7-dihydro-9-(4-ethoxyphenyl)-5H-benzocycloheptene 在 pyridinium hydrobromide perbromide 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以98%的产率得到3-(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenoxy)-6,7-dihydro-8-bromo-9-(4-ethoxyphenyl)-5H-benzocycloheptene
  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