N-methylamide 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-dione-2-carboxylic acid | 1147123-80-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: N-methylamide 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-dione-2-carboxylic acid
• CAS: 1147123-80-5
• 化学式: C₂₀H₁₅NO₅S
• 分子量: 381.409
• InChiKey: SKTXATYKSMCASN-UHFFFAOYSA-N

物化性质

• 熔点：
  >250 °C
• 沸点：
  694.3±55.0 °C(predicted)
• 密度：
  1.407±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  27.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  81.7
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-methylamide 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-dione-2-carboxylic acid 、 羟乙基乙二胺 生成 N-methylamide 4,11-bis[{2-[(2-hydroxyethyl)amino]ethyl}amino]anthra[2,3-b]thiophene-5,10-dione-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones

  摘要：

  We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b] thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b] thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53 (-/-) cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b] thiophene-5,10-dione derivatives. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.01.047
• 作为产物：
  描述：

  4,11-dimethoxyanthra[2,3-b]thiophene-5,10-dione-2-carboxylic acid 、 盐酸甲胺 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.33h， 以90%的产率得到N-methylamide 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-dione-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones

  摘要：

  We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b] thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b] thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53 (-/-) cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b] thiophene-5,10-dione derivatives. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.01.047