(S)-1-[2-(dimethylamino)ethylamino]-4-[2-(2-hydroxymethylpyrrolidin-1-yl)ethylamino]-5,8-dihydroxyanthracene-9,10-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: (S)-1-[2-(dimethylamino)ethylamino]-4-[2-(2-hydroxymethylpyrrolidin-1-yl)ethylamino]-5,8-dihydroxyanthracene-9,10-dione
• 英文别名: 1-[2-(dimethylamino)ethylamino]-5,8-dihydroxy-4-[2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]ethylamino]anthracene-9,10-dione
• 化学式: C₂₅H₃₂N₄O₅
• 分子量: 468.553
• InChiKey: YZDDEFHDOOFIFU-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  125
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  L-脯氨醇 在 吡啶 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 生成 (S)-1-[2-(dimethylamino)ethylamino]-4-[2-(2-hydroxymethylpyrrolidin-1-yl)ethylamino]-5,8-dihydroxyanthracene-9,10-dione
  参考文献：
  名称：

  Development of Nonsymmetrical 1,4-Disubstituted Anthraquinones That Are Potently Active against Cisplatin-Resistant Ovarian Cancer Cells

  摘要：

  A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropylamino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.

  DOI：

  10.1021/jm050438f

文献信息

• Development of Nonsymmetrical 1,4-Disubstituted Anthraquinones That Are Potently Active against Cisplatin-Resistant Ovarian Cancer Cells
  作者：Klaus Pors、Jane A. Plumb、Robert Brown、Paul Teesdale-Spittle、Mark Searcey、Paul J. Smith、Laurence H. Patterson

  DOI：10.1021/jm050438f

  日期：2005.10.1

  A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropylamino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.