D,L-1,2-bis(2,6-difluoro-3-methoxyphenyl)ethylenediamine

• 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: D,L-1,2-bis(2,6-difluoro-3-methoxyphenyl)ethylenediamine
• 英文别名: (1S,2S)-1,2-bis(2,6-difluoro-3-methoxyphenyl)ethane-1,2-diamine
• 化学式: C₁₆H₁₆F₄N₂O₂
• 分子量: 344.309
• InChiKey: ITUBJMYQUDIFAZ-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  D,L-1,2-bis(2,6-difluoro-3-methoxyphenyl)ethylenediamine 在 正丁基锂 、 三溴化硼 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 5.25h， 生成 D,L-N,N'-diethyl-1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine
  参考文献：
  名称：

  [N-Ethyl- and [N,N‘-Diethyl-1,2-bis(2,6-difluoro-3-hydroxyphenyl)- ethylenediamine]dichloroplatinum(II):  Structure and Cytotoxic/Estrogenic Activity in Breast Cancer Cells

  摘要：

  N-Ethyl and N,N'-diethyl derivatives (erythro- and threo-2-PtCl2; meso- and D,L-3-PtCl2) of [meso- and D,L-1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (meso- and D,L-1-PtCl2) were synthesized and tested for cytotoxicity on the estrogen receptor-positive (ER+) human MCF-7 breast cancer cell line. In this test, only D,L-1-PtCl2 and threo2-PtCl2 showed strong cytotoxic properties. This revealed the existence of at least one NH2 fragment as a prerequisite for antitumor activity. Furthermore, studies on the three-dimensional structure of the new compounds demonstrated that the aryl and alkyl residues at the five-membered chelate ring have to be arranged in equatorial positions for the triggering of cytotoxic effects, very likely due to the reaction with d(GpG) sequences in DNA resulting in GG-N7,N7 chelates. A contribution of the ER-mediated processes-(a) hindrance of the cellular processing of Pt-modified DNA by overexpression of high mobility group domain proteins and (b) interruption of the vicious circle of mutual growth stimulation of breast cancer cells and granulocytes/macrophages by reduction of the formation of key cytokines-to the anti-breast cancer activity of threo-2-PtCl2 is unlikely, since we did not observe transcription activation in the test on ER+ MCF-7 breast cancer cells stably transfected with luciferase reporter plasmid ERE(wtc)luc.

  DOI：

  10.1021/jm050186i
• 作为产物：
  描述：

  2,4-二氟苯甲醚 在 硫酸 、 仲丁基锂 作用下， 以 乙腈 为溶剂， 反应 3.25h， 生成 D,L-1,2-bis(2,6-difluoro-3-methoxyphenyl)ethylenediamine
  参考文献：
  名称：

  Synthesis and evaluation of the anti-mammary tumor activity and of the estrogenic side effects of [1,2-bis(2,6-dihalo-3-hydroxyphenyl)ethylenediamine]platinum(II) complexes

  摘要：

  The synthesis and structural characterization of mammary tumor-inhibiting, diastereomeric [1,2-bis(2,6-dihalo-3-hydroxyphenyl) ethylenediamine]platinum(II) complexes with 2,6-Cl2, 2-F, 6-Cl, 2-Cl, 6-F and 2,6-F2 substituents (1-PtSO4 to 4-PtSO4) are described. The related 1,2-diphenylethylenediamines (1-4) are synthesized by stereoselective meso-meso and D,L-D,L diaza-Cope-rearrangement reactions and coordinated to platinum(II) with K2PtI4 (1-PtI2 to 4-PtI2). The subsequent reaction with Ag2SO4 leads to the respective sulfatoplatinum(II) complexes. They were tested for their anti-tumor activities on die hormone-sensitive and- insensitive MXT mammary carcinoma implanted in mice (MXT-MC, ER+ and MXT-MC, ER-). Complexes with F atoms in the neighborhood of the 3-hydroxy group showed strong inhibitory effects on the MXT-MC, ER+. The best effects were found for the diastereomeric 2,6-F2-substituted complexes, meso-4-PtSO4 and D,L-4-PtSO4. These complexes are strongly active both on the MXT-MC, ER+ and the MXT-MC, ER- and cause no estrogenic side effects.

  DOI：

  10.1016/0223-5234(93)90003-w

文献信息

• Synthesis and evaluation of the anti-mammary tumor activity and of the estrogenic side effects of [1,2-bis(2,6-dihalo-3-hydroxyphenyl)ethylenediamine]platinum(II) complexes
  作者：R Gust、H Schönenberger

  DOI：10.1016/0223-5234(93)90003-w

  日期：1993.1

  The synthesis and structural characterization of mammary tumor-inhibiting, diastereomeric [1,2-bis(2,6-dihalo-3-hydroxyphenyl) ethylenediamine]platinum(II) complexes with 2,6-Cl2, 2-F, 6-Cl, 2-Cl, 6-F and 2,6-F2 substituents (1-PtSO4 to 4-PtSO4) are described. The related 1,2-diphenylethylenediamines (1-4) are synthesized by stereoselective meso-meso and D,L-D,L diaza-Cope-rearrangement reactions and coordinated to platinum(II) with K2PtI4 (1-PtI2 to 4-PtI2). The subsequent reaction with Ag2SO4 leads to the respective sulfatoplatinum(II) complexes. They were tested for their anti-tumor activities on die hormone-sensitive and- insensitive MXT mammary carcinoma implanted in mice (MXT-MC, ER+ and MXT-MC, ER-). Complexes with F atoms in the neighborhood of the 3-hydroxy group showed strong inhibitory effects on the MXT-MC, ER+. The best effects were found for the diastereomeric 2,6-F2-substituted complexes, meso-4-PtSO4 and D,L-4-PtSO4. These complexes are strongly active both on the MXT-MC, ER+ and the MXT-MC, ER- and cause no estrogenic side effects.
• [<i>N</i>-Ethyl- and [<i>N</i>,<i>N</i>‘-Diethyl-1,2-bis(2,6-difluoro-3-hydroxyphenyl)- ethylenediamine]dichloroplatinum(II):  Structure and Cytotoxic/Estrogenic Activity in Breast Cancer Cells
  作者：Ronald Gust、Karlheinz Niebler、Helmut Schönenberger

  DOI：10.1021/jm050186i

  日期：2005.11.1

  N-Ethyl and N,N'-diethyl derivatives (erythro- and threo-2-PtCl2; meso- and D,L-3-PtCl2) of [meso- and D,L-1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (meso- and D,L-1-PtCl2) were synthesized and tested for cytotoxicity on the estrogen receptor-positive (ER+) human MCF-7 breast cancer cell line. In this test, only D,L-1-PtCl2 and threo2-PtCl2 showed strong cytotoxic properties. This revealed the existence of at least one NH2 fragment as a prerequisite for antitumor activity. Furthermore, studies on the three-dimensional structure of the new compounds demonstrated that the aryl and alkyl residues at the five-membered chelate ring have to be arranged in equatorial positions for the triggering of cytotoxic effects, very likely due to the reaction with d(GpG) sequences in DNA resulting in GG-N7,N7 chelates. A contribution of the ER-mediated processes-(a) hindrance of the cellular processing of Pt-modified DNA by overexpression of high mobility group domain proteins and (b) interruption of the vicious circle of mutual growth stimulation of breast cancer cells and granulocytes/macrophages by reduction of the formation of key cytokines-to the anti-breast cancer activity of threo-2-PtCl2 is unlikely, since we did not observe transcription activation in the test on ER+ MCF-7 breast cancer cells stably transfected with luciferase reporter plasmid ERE(wtc)luc.