2,6-Bis-(2-dimethylamino-ethyl)-2H-1,2,6,7a-tetraaza-benzo[fg]aceanthrylene-5,7-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2,6-Bis-(2-dimethylamino-ethyl)-2H-1,2,6,7a-tetraaza-benzo[fg]aceanthrylene-5,7-dione
• 英文别名: 10,16-Bis[2-(dimethylamino)ethyl]-1,9,10,16-tetrazapentacyclo[9.6.2.02,7.08,19.014,18]nonadeca-2,4,6,8,11(19),12,14(18)-heptaene-15,17-dione
• 化学式: C₂₃H₂₆N₆O₂
• 分子量: 418.498
• InChiKey: MHKVVLLUWFCOIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  64.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-肼基-N,N-二甲基-乙胺 、 6-chloro-2-[2-(dimethylamino)ethyl]-2,3-dihydro-1H,7H-pyrimido [5,6,1-de]acridine-1,3,7-trione 以 乙二醇乙醚 为溶剂， 以80%的产率得到2,6-Bis-(2-dimethylamino-ethyl)-2H-1,2,6,7a-tetraaza-benzo[fg]aceanthrylene-5,7-dione
  参考文献：
  名称：

  2,6-Di(ω-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-mn]pyrimido[5,6,1-de]acridine-5,7-diones:  Novel, Potent, Cytotoxic, and DNA-Binding Agents

  摘要：

  DNA-binding agents with potential antitumor activities bearing two cationic side chains, the 2,6-di(omega-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-mn]pyrimido[5,6,1-de]acridine-5,7-diones (4a-r), have been prepared either by reaction of the appropriate 2-(omega-aminoalkyl)-6-chloro-2,3-dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione with the appropriate (omega-aminoalkyl)hydrazine or by cyclization of the requisite N-6,2-di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-6-carboxamide with phosgene. In vitro cytotoxic properties of these derivatives against three human colon adenocarcinoma cell lines (HT29, LoVo, and LoVo/Dx) and against some cell lines of the NCI panel are described and compared to that of reference drugs. Some of the new compounds showed outstanding potency while lacking cross-resistance with anthracyclines. Structure-activity relationships are discussed, and a mechanistic analysis is performed using the COMPARE procedure. The mechanism and efficiency of noncovalent DNA binding of these compounds are examined using gel electrophoresis and fluorometric techniques. The 2,6-di(omega-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-mn]pyrimido[5,6,1-de]acridine-5,7-diones (4) constitute a new class of potent, cytotoxic DNA-binding agents not cross-resistant with doxorubicin.

  DOI：

  10.1021/jm011004x

文献信息

• 2,6-Di(ω-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-<i>mn</i>]pyrimido[5,6,1-<i>de</i>]acridine-5,7-diones:  Novel, Potent, Cytotoxic, and DNA-Binding Agents
  作者：Ippolito Antonini、Paolo Polucci、Amelia Magnano、Barbara Gatto、Manlio Palumbo、Ernesto Menta、Nicoletta Pescalli、Sante Martelli

  DOI：10.1021/jm011004x

  日期：2002.1.1

  DNA-binding agents with potential antitumor activities bearing two cationic side chains, the 2,6-di(omega-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-mn]pyrimido[5,6,1-de]acridine-5,7-diones (4a-r), have been prepared either by reaction of the appropriate 2-(omega-aminoalkyl)-6-chloro-2,3-dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione with the appropriate (omega-aminoalkyl)hydrazine or by cyclization of the requisite N-6,2-di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-6-carboxamide with phosgene. In vitro cytotoxic properties of these derivatives against three human colon adenocarcinoma cell lines (HT29, LoVo, and LoVo/Dx) and against some cell lines of the NCI panel are described and compared to that of reference drugs. Some of the new compounds showed outstanding potency while lacking cross-resistance with anthracyclines. Structure-activity relationships are discussed, and a mechanistic analysis is performed using the COMPARE procedure. The mechanism and efficiency of noncovalent DNA binding of these compounds are examined using gel electrophoresis and fluorometric techniques. The 2,6-di(omega-aminoalkyl)-2,5,6,7-tetrahydropyrazolo[3,4,5-mn]pyrimido[5,6,1-de]acridine-5,7-diones (4) constitute a new class of potent, cytotoxic DNA-binding agents not cross-resistant with doxorubicin.