6-amino-9-[3,7-bis(N,N'-bis-tert-butoxycarbonyldiaminomethylene)-11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triaza-undecyl]-9H-purine

• 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-[3,7-bis(N,N'-bis-tert-butoxycarbonyldiaminomethylene)-11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triaza-undecyl]-9H-purine
• 英文别名: tert-butyl N-[[3-[2-(6-aminopurin-9-yl)ethyl-[N,N'-bis[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]amino]propyl-[3-[(6-chloro-2-methoxyacridin-9-yl)amino]propyl]amino]-[(2-methylpropan-2-yl)oxycarbonylamino]methylidene]carbamate
• 化学式: C₄₉H₆₈ClN₁₃O₉
• 分子量: 1018.61
• InChiKey: CZQGBCJJWACSAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  72
• 可旋转键数：
  25
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  264
• 氢给体数：
  4
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  6-amino-9-[3,7-bis(N,N'-bis-tert-butoxycarbonyldiaminomethylene)-11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triaza-undecyl]-9H-purine 在 盐酸 、 溶剂黄146 作用下， 反应 30.0h， 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：

  N,N′-二-Boc-硫脲 、 6-amino-9-[11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triazaundecyl]-9H-purine 在 三乙胺 、 mercury dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以52%的产率得到6-amino-9-[3,7-bis(N,N'-bis-tert-butoxycarbonyldiaminomethylene)-11-(6-chloro-2-methoxyacridin-9-yl)-3,7,11-triaza-undecyl]-9H-purine
  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

文献信息

• 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.