6-amino-9-[11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triazaundecyl]-9H-purine | 114882-26-7

• 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-amino-9-[11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triazaundecyl]-9H-purine
• 英文别名: N'-[2-(6-aminopurin-9-yl)ethyl]-N-[3-[(6-chloro-2-methoxyacridin-9-yl)amino]propyl]propane-1,3-diamine
• CAS: 114882-26-7
• 化学式: C₂₇H₃₂ClN₉O
• 分子量: 534.064
• InChiKey: VTURXBIULPGNBT-UHFFFAOYSA-N

物化性质

• 沸点：
  813.3±75.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-amino-9-[11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triazaundecyl]-9H-purine 在 盐酸 、 溶剂黄146 、 三乙胺 、 mercury dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 N-[2-(6-Amino-purin-9-yl)-ethyl]-N-(3-{N-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-guanidino}-propyl)-guanidine
  参考文献：
  名称：

  Abasic Site Recognition in DNA as a New Strategy To Potentiate the Action of Anticancer Alkylating Drugs?

  摘要：

  Inhibition of abasic site repair in the cell seems an attractive strategy to potentiate the action of antitumor DNA alkylating drugs. Molecules that bind specifically and strongly to the abasic site are possible candidates to achieve such inhibition. We explored this strategy by preparing molecule 4 that incorporates (1) an aminoacridine intercalator for DNA binding, (2) an adenine moiety for abasic site recognition, and (3) a linker containing two guanidinium functions to increase binding to DNA without inducing cleavage at the base-sensitive abasic site. Compound 4 was compared to analogues containing secondary amines, i.e., 1. We report on synthesis of the new heterodimer 4. We show by physicochemical studies-including determination of association constants with calf-thymus DNA, T-m measurements, and high-field NMR examination of the complexes formed with abasic DNA duplexes-that 4 binds specifically and more strongly to the abasic site than the analogues. Compound 4 does not cleave abasic plasmid DNA. Compound 4 shows apparent synergy with the anticancer bischloroethylnitrosourea (BCNU) in L1210 and A549 cell lines in vitro. It potentiates BCNU in the in vivo tests. The results favor the pertinence of the strategy.

  DOI：

  10.1021/jm9901428
• 作为产物：
  描述：

  6,9-二氯-2-甲氧基吖啶 、 6-amino-9-(10-amino-3,7-diazadecyl)-9H-purine 在 三乙胺 作用下， 以 苯酚 为溶剂， 生成 6-amino-9-[11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triazaundecyl]-9H-purine
  参考文献：
  名称：

  The abasic site as a target for generation of locally multiply damaged sites

  摘要：

  Abasic sites in DNA have been specifically targeted by synthetic compounds able to cleave DNA at abasic sites and to induce photodamages in the vicinity of the lesion. The synthesis and the photoactivity of the drugs on abasic sites containing DNA and oligonucleotides are reported. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00081-0

文献信息

• A new class of artificial nucleases that recognize and cleave apurinic sites in DNA with great selectivity and efficiency
  作者：Abdellatif Fkyerat、Martine Demeunynck、Jean Francois Constant、Pierre Michon、Jean Lhomme

  DOI：10.1021/ja00075a011

  日期：1993.11

  A series of tailor-made molecules, 1 and 4-7, have been prepared to recognize and cleave DNA at apurinic sites. These molecules incorporate in their structure different units designed for specific functions: (1) an intercalator for DNA binding, (2) a nucleic base for abasic site recognition, and (3) a linker endowed with both a binding function and a cleavage function (Scheme II). The constituent units were varied successively in the series of molecules to get insight into their mode of action and prepare more active compounds. H-1 NMR spectroscopy reveals the absence of intramolecular ring-ring stacking interactions in water between the base and the intercalator in all molecules 1 and 4-7. All bind to calf thymus DNA with binding constants ranging from 10(4) to 10(6) M-1. Their nuclease activity was estimated by measuring their ability to induce single strand breaks in depurinated pBR 322 plasmid DNA. The most efficient molecule, 5, exhibits high recognition selectivity and cleavage efficiency: at nanomolar concentrations, 5 recognizes and cleaves the abasic lesion present in a DNA molecule containing an average of 1.8 apurinic sites in its 4 362 base pairs sequence. Molecule 5 exhibits higher cleaving efficiency than the reported tripeptide Lys-Trp-Lys: 10(-8) M concentrations of the former (5) lead to cleavage ratios comparable to those observed for the latter used as 10(-3) M concentration. This enzyme mimic 5 can be used advantageously as a substitute to the natural nuclease for in vitro cleavage of depurinated DNA.
• Abasic Site Recognition in DNA as a New Strategy To Potentiate the Action of Anticancer Alkylating Drugs?
  作者：Philippe Belmont、Muriel Jourdan、Martine Demeunynck、Jean-François Constant、Julian Garcia、Jean Lhomme、Danièle Carez、Alain Croisy

  DOI：10.1021/jm9901428

  日期：1999.12.1

  Inhibition of abasic site repair in the cell seems an attractive strategy to potentiate the action of antitumor DNA alkylating drugs. Molecules that bind specifically and strongly to the abasic site are possible candidates to achieve such inhibition. We explored this strategy by preparing molecule 4 that incorporates (1) an aminoacridine intercalator for DNA binding, (2) an adenine moiety for abasic site recognition, and (3) a linker containing two guanidinium functions to increase binding to DNA without inducing cleavage at the base-sensitive abasic site. Compound 4 was compared to analogues containing secondary amines, i.e., 1. We report on synthesis of the new heterodimer 4. We show by physicochemical studies-including determination of association constants with calf-thymus DNA, T-m measurements, and high-field NMR examination of the complexes formed with abasic DNA duplexes-that 4 binds specifically and more strongly to the abasic site than the analogues. Compound 4 does not cleave abasic plasmid DNA. Compound 4 shows apparent synergy with the anticancer bischloroethylnitrosourea (BCNU) in L1210 and A549 cell lines in vitro. It potentiates BCNU in the in vivo tests. The results favor the pertinence of the strategy.
• The abasic site as a target for generation of locally multiply damaged sites
  作者：Alain Martelli、Nathalie Berthet、Jean-François Constant、Martine Demeunynck、Jean Lhomme

  DOI：10.1016/s0960-894x(00)00081-0

  日期：2000.4

  Abasic sites in DNA have been specifically targeted by synthetic compounds able to cleave DNA at abasic sites and to induce photodamages in the vicinity of the lesion. The synthesis and the photoactivity of the drugs on abasic sites containing DNA and oligonucleotides are reported. (C) 2000 Elsevier Science Ltd. All rights reserved.