4,11-bis(2-aminoethylamino)-2-methylanthra[2,3-b]furan-5,10-dione | 1263864-35-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 4,11-bis(2-aminoethylamino)-2-methylanthra[2,3-b]furan-5,10-dione
• 英文别名: 4,11-Bis(2-aminoethylamino)-2-methylnaphtho[2,3-f][1]benzofuran-5,10-dione
• CAS: 1263864-35-2
• 化学式: C₂₁H₂₂N₄O₃
• 分子量: 378.431
• InChiKey: PIWNIIWKOQPONH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4,11-bis(2-aminoethylamino)-2-methylanthra[2,3-b]furan-5,10-dione 在 盐酸 作用下， 以 水 为溶剂， 以0.13 g的产率得到4,11-bis(2-aminoethylamino)-2-methylanthra[2,3-b]furan-5,10-dione dihydrochloride
  参考文献：
  名称：

  The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10-diones: Synthesis and anti-proliferative characteristics

  摘要：

  We developed the synthesis of a series of furan-fused tetracyclic analogues of the antitumor agent ametantrone. The reactions included nucleophilic substitution of propoxy groups in 4,11-dipropoxyanthra[2,3-b]furan-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra [2,3-b]furan-5,10-dione in good yields. Studies of anti-proliferative activity on a panel of mammalian tumor cell lines demonstrated that anthra[2,3-b]furan-5,10-diones were the most potent derivatives among heteroarene-fused ametantrone analogues with one heteroatom. We identified several compounds that evoked a growth inhibitory effect at submicromolar concentrations. The anthra[2,3-b] furan-5,10-dione 9 with distal methylamino groups was markedly potent against drug-resistant cell lines with P-glycoprotein overexpression or p53 gene deletion. Furthermore, this derivative attenuated in vitro topoisomerase I-mediated DNA uncoiling at low micromolar concentrations. These results demonstrate that anthrafurandiones are a new class of heterocyclic anthraquinone derivatives with the properties potentially valuable for anticancer therapy. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.017
• 作为产物：
  描述：

  2-methyl-4,11-dipropoxyanthra[2,3-b]furan-5,10-dione 、 乙二胺 生成 4,11-bis(2-aminoethylamino)-2-methylanthra[2,3-b]furan-5,10-dione
  参考文献：
  名称：

  The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10-diones: Synthesis and anti-proliferative characteristics

  摘要：

  We developed the synthesis of a series of furan-fused tetracyclic analogues of the antitumor agent ametantrone. The reactions included nucleophilic substitution of propoxy groups in 4,11-dipropoxyanthra[2,3-b]furan-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra [2,3-b]furan-5,10-dione in good yields. Studies of anti-proliferative activity on a panel of mammalian tumor cell lines demonstrated that anthra[2,3-b]furan-5,10-diones were the most potent derivatives among heteroarene-fused ametantrone analogues with one heteroatom. We identified several compounds that evoked a growth inhibitory effect at submicromolar concentrations. The anthra[2,3-b] furan-5,10-dione 9 with distal methylamino groups was markedly potent against drug-resistant cell lines with P-glycoprotein overexpression or p53 gene deletion. Furthermore, this derivative attenuated in vitro topoisomerase I-mediated DNA uncoiling at low micromolar concentrations. These results demonstrate that anthrafurandiones are a new class of heterocyclic anthraquinone derivatives with the properties potentially valuable for anticancer therapy. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.017

文献信息

• Bis(chloroacetamidino)-Derived Heteroarene-Fused Anthraquinones Bind to and Cause Proteasomal Degradation of tNOX, Leading to c-Flip Downregulation and Apoptosis in Oral Cancer Cells
  作者：Jeng Shiun Chang、Chien-Yu Chen、Alexander S. Tikhomirov、Atikul Islam、Ru-Hao Liang、Chia-Wei Weng、Wei-Hou Wu、Andrey E. Shchekotikhin、Pin Ju Chueh

  DOI：10.3390/cancers14194719

  日期：——

  Anthraquinone-based intercalating compounds, namely doxorubicin and mitoxantrone, have been used clinically based on their capacity to bind DNA and induce DNA damage. However, their applications have been limited by side effects and drug resistance. New-generation anthraquinone derivatives fused with different heterocycles have been chemically synthesized and screened for higher anticancer potency. Among the

  基于蒽醌的嵌入化合物，即阿霉素和米托蒽醌，基于它们结合 DNA 和诱导 DNA 损伤的能力，已在临床上使用。然而，它们的应用受到副作用和耐药性的限制。已经化学合成了与不同杂环稠合的新一代蒽醌衍生物，并筛选了更高的抗癌效力。在我们之前的研究中报道的化合物中，发现 4,11-双（2-（2-氯乙脒）乙基氨基）蒽[2,3-b]噻吩-5,10-二酮二盐酸盐（命名为 2c）具有凋亡作用，但是导致细胞毒性的直接细胞靶点仍然未知。在这里，我们报告了另外两种衍生物 4,11-bis(2-(2-chloroacetamidine)ethylamino)naphtho[2,3-f]indole-5,10-dione dihydrochloride (2a) 和 4 , 11-双(2-(2-氯乙脒)乙基氨基)-2-甲基蒽[2,3-b]呋喃-5,10-二酮二盐酸盐(2b)。我们试图使用分子对接模拟和细胞热位移分析 (CETSA)
• The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10-diones: Synthesis and anti-proliferative characteristics
  作者：Andrey E. Shchekotikhin、Valeria A. Glazunova、Lyubov G. Dezhenkova、Elena K. Shevtsova、Valery F. Traven’、Jan Balzarini、Hsu-Shan Huang、Alexander A. Shtil、Maria N. Preobrazhenskaya

  DOI：10.1016/j.ejmech.2010.11.017

  日期：2011.1

  We developed the synthesis of a series of furan-fused tetracyclic analogues of the antitumor agent ametantrone. The reactions included nucleophilic substitution of propoxy groups in 4,11-dipropoxyanthra[2,3-b]furan-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra [2,3-b]furan-5,10-dione in good yields. Studies of anti-proliferative activity on a panel of mammalian tumor cell lines demonstrated that anthra[2,3-b]furan-5,10-diones were the most potent derivatives among heteroarene-fused ametantrone analogues with one heteroatom. We identified several compounds that evoked a growth inhibitory effect at submicromolar concentrations. The anthra[2,3-b] furan-5,10-dione 9 with distal methylamino groups was markedly potent against drug-resistant cell lines with P-glycoprotein overexpression or p53 gene deletion. Furthermore, this derivative attenuated in vitro topoisomerase I-mediated DNA uncoiling at low micromolar concentrations. These results demonstrate that anthrafurandiones are a new class of heterocyclic anthraquinone derivatives with the properties potentially valuable for anticancer therapy. (C) 2010 Elsevier Masson SAS. All rights reserved.