6-chloro-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione | 220250-19-1

• 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: 6-chloro-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione
• 英文别名: 10-Chloro-15-[3-(dimethylamino)propyl]-1,15-diazatetracyclo[7.7.1.02,7.013,17]heptadeca-2,4,6,9,11,13(17)-hexaene-8,14,16-trione
• CAS: 220250-19-1
• 化学式: C₂₀H₁₈ClN₃O₃
• 分子量: 383.834
• InChiKey: BIRJFNRQKILHLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  60.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione 在 三乙胺 作用下， 以 乙二醇乙醚 为溶剂， 反应 4.0h， 生成 15-[3-(Dimethylamino)propyl]-10-[3-[methyl-[3-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)propyl]amino]propylamino]-1,15-diazatetracyclo[7.7.1.02,7.013,17]heptadeca-2,4,6,9,11,13(17)-hexaene-8,14,16-trione
  参考文献：
  名称：

  Synthesis and Biological Evaluation of New Asymmetrical Bisintercalators as Potential Antitumor Drugs

  摘要：

  The good results obtained in the past decade with various types of potential bisintercalating agents, e. g., LU 79553, DMP 840, BisBFI, MCI3335, WMC-26, BisAC, BisPA, and the asymmetrical derivative WMC-79 ( Chart 1), prompted us to investigate a new series of asymmetrical bisintercalators, compounds 1a-t ( Chart 2), which can combine the potentiality of bisintercalation with a possible different mechanism of action due to two diverse chromophores. The DNA-binding properties of these compounds have been examined using fluorometric techniques: target compounds are excellent DNA ligands, with a clear preference for binding to AT-rich duplexes. In vitro cytotoxicity of these derivatives toward human hormone-refractory prostate adenocarcinoma cell line (PC-3) is described. Apoptosis assays of four selected compounds are also reported. Very potent cytotoxic compounds, some of them capable of inducing early apoptosis, have been identified.

  DOI：

  10.1021/jm0606793
• 作为产物：
  描述：

  光气 、 N5-[3-(dimethylamino)propyl]-2-[2-(dimethylamino)ethyl]-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamide 在 三乙胺 作用下， 以 氯仿 、 甲苯 为溶剂， 反应 0.25h， 以79%的产率得到6-chloro-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione
  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.
• Synthesis and Biological Evaluation of New Asymmetrical Bisintercalators as Potential Antitumor Drugs
  作者：Ippolito Antonini、Giorgio Santoni、Roberta Lucciarini、Consuelo Amantini、Silvia Sparapani、Amelia Magnano

  DOI：10.1021/jm0606793

  日期：2006.11.30

  The good results obtained in the past decade with various types of potential bisintercalating agents, e. g., LU 79553, DMP 840, BisBFI, MCI3335, WMC-26, BisAC, BisPA, and the asymmetrical derivative WMC-79 ( Chart 1), prompted us to investigate a new series of asymmetrical bisintercalators, compounds 1a-t ( Chart 2), which can combine the potentiality of bisintercalation with a possible different mechanism of action due to two diverse chromophores. The DNA-binding properties of these compounds have been examined using fluorometric techniques: target compounds are excellent DNA ligands, with a clear preference for binding to AT-rich duplexes. In vitro cytotoxicity of these derivatives toward human hormone-refractory prostate adenocarcinoma cell line (PC-3) is described. Apoptosis assays of four selected compounds are also reported. Very potent cytotoxic compounds, some of them capable of inducing early apoptosis, have been identified.