ethyl (2-(4-(3-methoxy-8-phenyl-6,7-dihydro-5H-benzocyclohepten-9-yl)phenoxy)ethyl)(N-methyl)carbamate | 1610422-79-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: ethyl (2-(4-(3-methoxy-8-phenyl-6,7-dihydro-5H-benzocyclohepten-9-yl)phenoxy)ethyl)(N-methyl)carbamate
• CAS: 1610422-79-1
• 化学式: C₃₀H₃₃NO₄
• 分子量: 471.596
• InChiKey: CWEZPDDYYYEUOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.46
• 重原子数：
  35.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  48.0
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl (2-(4-(3-methoxy-8-phenyl-6,7-dihydro-5H-benzocyclohepten-9-yl)phenoxy)ethyl)(N-methyl)carbamate 在 吡啶盐酸盐 作用下， 反应 3.0h， 以41%的产率得到9-(4-(2-(methylamino)ethoxy)phenyl)-8-phenyl-6,7-dihydro-5H-benzocyclohepten-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：

  N-ethoxycarbonyl-N-methyl-2-aminoethanol 、 3-methoxy-6,7-dihydro-8-phenyl-9-(4-hydroxyphenyl)-5H-benzocycloheptene 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以39%的产率得到ethyl (2-(4-(3-methoxy-8-phenyl-6,7-dihydro-5H-benzocyclohepten-9-yl)phenoxy)ethyl)(N-methyl)carbamate
  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