1-Chloro-9-oxo-9,10-dihydro-acridine-4-carboxylic acid [2-(2-hydroxy-ethylamino)-ethyl]-amide | 197304-40-8

• 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: 1-Chloro-9-oxo-9,10-dihydro-acridine-4-carboxylic acid [2-(2-hydroxy-ethylamino)-ethyl]-amide
• 英文别名: 1-chloro-N-[2-(2-hydroxyethylamino)ethyl]-9-oxo-10H-acridine-4-carboxamide
• CAS: 197304-40-8
• 化学式: C₁₈H₁₈ClN₃O₃
• 分子量: 359.812
• InChiKey: FRIKMLIDNQWGKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  90.5
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-肼基-N,N-二甲基-乙胺 、 1-Chloro-9-oxo-9,10-dihydro-acridine-4-carboxylic acid [2-(2-hydroxy-ethylamino)-ethyl]-amide 以 乙二醇乙醚 为溶剂， 以46%的产率得到2-(2-Dimethylamino-ethyl)-2,6-dihydro-pyrazolo[3,4,5-kl]acridine-5-carboxylic acid [2-(2-hydroxy-ethylamino)-ethyl]-amide
  参考文献：
  名称：

  Synthesis, Antitumor Cytotoxicity, and DNA-Binding of Novel N-5,2-Di(ω-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides

  摘要：

  A series of DNA-binding potential antitumor agents bearing a cationic carboxamide side chain attached in position peri to an electron-withdrawing atom, N-5,2-di(omega -aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides, has been prepared by reaction of the appropriate 1-chloro-9-oxo-9,10-dihyclro-4-acridinecarboxamides with the suitable (omega -aminoalkyl)-hydrazine. The noncovalent DNA-binding properties of these compounds have been examined using a fluorometric technique. In vitro cytotoxic potency of these derivatives toward the human colon adenocarcinoma cell line (HT29) is described and compared to that of reference drugs. Structure-activity relationships are discussed. Two highly DNA-affinic and potent cytotoxic compounds, 4m,o, have been identified as new leads in the antitumor strategies.

  DOI：

  10.1021/jm010917o
• 作为产物：
  描述：

  1-氯-9,10-二氢-9-氧代-4-吖啶羧酸 在 盐酸 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 1-Chloro-9-oxo-9,10-dihydro-acridine-4-carboxylic acid [2-(2-hydroxy-ethylamino)-ethyl]-amide
  参考文献：
  名称：

  1-[（ω-氨基烷基）氨基] -4- [N-（ω-氨基烷基）氨基甲酰基] -9-氧代-9，10-二氢ac啶类作为插入细胞毒剂：合成，DNA结合和生物学评估。

  摘要：

  一系列的DNA嵌入潜在的抗肿瘤药1-[（（ω-氨基烷基）氨基] -4- [N-（ω-氨基烷基）氨基甲酰基] -9-oxo-9，10-二氢ac啶，已经通过氨解法制备。相应的4- [N-（ω-氨基烷基）氨基甲酰基] -1-氯衍生物与合适的ω-氨基烷基胺。这些双功能化的化合物的非共价DNA结合特性已使用荧光和热变性技术的组合进行了检查，并与已建立的DNA嵌入剂和阳离子小沟配体的行为进行了比较。结果表明（i）这些药物的DNA亲和力比功能化程度较低的a啶酮高得多，其“表观”结合常数为（0.1-2.1）x 10（7）和（0.3-7.5）x 10（7）M- pH分别为5和7时为1，（ii）整体亲和力对柔性侧链的长度和所连接的胺取代基的复杂度均敏感，并且（iii）侧链侧链影响向中等AT优先结合的转换。尽管对某些化合物而言，很差的相关性，但对六种肿瘤细胞系的体外细胞毒性作用与观察到的DNA亲和力大致相似。还

  DOI：

  10.1021/jm970114u

文献信息

• Synthesis, Antitumor Cytotoxicity, and DNA-Binding of Novel <i>N-</i>5,2-Di(ω-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-<i>kl</i>]acridine-5-carboxamides
  作者：Ippolito Antonini、Paolo Polucci、Amelia Magnano、Sante Martelli

  DOI：10.1021/jm010917o

  日期：2001.9.1

  A series of DNA-binding potential antitumor agents bearing a cationic carboxamide side chain attached in position peri to an electron-withdrawing atom, N-5,2-di(omega -aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides, has been prepared by reaction of the appropriate 1-chloro-9-oxo-9,10-dihyclro-4-acridinecarboxamides with the suitable (omega -aminoalkyl)-hydrazine. The noncovalent DNA-binding properties of these compounds have been examined using a fluorometric technique. In vitro cytotoxic potency of these derivatives toward the human colon adenocarcinoma cell line (HT29) is described and compared to that of reference drugs. Structure-activity relationships are discussed. Two highly DNA-affinic and potent cytotoxic compounds, 4m,o, have been identified as new leads in the antitumor strategies.
• 1-[(ω-Aminoalkyl)amino]-4-[<i>N</i>-(ω-aminoalkyl)carbamoyl]-9-oxo-9,10-dihydro- acridines as Intercalating Cytotoxic Agents:  Synthesis, DNA Binding, and Biological Evaluation
  作者：Ippolito Antonini、Paolo Polucci、Terence C. Jenkins、Lloyd R. Kelland、Ernesto Menta、Nicoletta Pescalli、Barbara Stefanska、Jan Mazerski、Sante Martelli

  DOI：10.1021/jm970114u

  日期：1997.11.1

  A series of DNA-intercalating potential antitumor agents, 1-[(omega-aminoalkyl)amino]-4-[N-(omega-aminoalkyl)carbamoyl]-9-oxo-9, 10-dihydroacridines, has been prepared by aminolysis of the corresponding 4-[N-(omega-aminoalkyl)carbamoyl]-1-chloro derivative with a suitable omega-aminoalkylamine. The noncovalent DNA-binding properties of these bis-functionalized compounds have been examined using a combination

  一系列的DNA嵌入潜在的抗肿瘤药1-[（（ω-氨基烷基）氨基] -4- [N-（ω-氨基烷基）氨基甲酰基] -9-oxo-9，10-二氢ac啶，已经通过氨解法制备。相应的4- [N-（ω-氨基烷基）氨基甲酰基] -1-氯衍生物与合适的ω-氨基烷基胺。这些双功能化的化合物的非共价DNA结合特性已使用荧光和热变性技术的组合进行了检查，并与已建立的DNA嵌入剂和阳离子小沟配体的行为进行了比较。结果表明（i）这些药物的DNA亲和力比功能化程度较低的a啶酮高得多，其“表观”结合常数为（0.1-2.1）x 10（7）和（0.3-7.5）x 10（7）M- pH分别为5和7时为1，（ii）整体亲和力对柔性侧链的长度和所连接的胺取代基的复杂度均敏感，并且（iii）侧链侧链影响向中等AT优先结合的转换。尽管对某些化合物而言，很差的相关性，但对六种肿瘤细胞系的体外细胞毒性作用与观察到的DNA亲和力大致相似。还