ethyl N-[N'-[3-(dimethylamino)propyl]-N-[6-[[N'-[3-(dimethylamino)propyl]-N-ethoxycarbonylcarbamimidoyl]amino]acridin-3-yl]carbamimidoyl]carbamate | 1071817-01-0

• 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: ethyl N-[N'-[3-(dimethylamino)propyl]-N-[6-[[N'-[3-(dimethylamino)propyl]-N-ethoxycarbonylcarbamimidoyl]amino]acridin-3-yl]carbamimidoyl]carbamate
• CAS: 1071817-01-0
• 化学式: C₃₁H₄₅N₉O₄
• 分子量: 607.756
• InChiKey: WEKGHTDSWLEVSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  44
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl N-[N'-[3-(dimethylamino)propyl]-N-[6-[[N'-[3-(dimethylamino)propyl]-N-ethoxycarbonylcarbamimidoyl]amino]acridin-3-yl]carbamimidoyl]carbamate 在 三甲基溴硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以84%的产率得到3,6-bis[3-(dimethylaminopropyl)guanidino]acridine
  参考文献：
  名称：

  Synthesis of N-acridinyl-N′-alkylguanidines: Dramatic influence of amine to guanidine replacement on the physicochemical properties

  摘要：

  Transformation of aminoacridines into N-acridinyl-N'-alkylguanidines is described. The chosen procedure allows introduction of pendent substituents (exemplified by N,N-dimethylaminopropyl chain) into key acridinyl thioureas, thus opening the way to structural diversity. Spectroscopic study and pK(a) determination show that the presence of the strongly basic guanidine has a dramatic influence on the ionization of the acridine nucleus by lowering the pk(a) value down to 4.49. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.100
• 作为产物：
  描述：

  N,N-二甲基-1,3-二氨基丙烷 、 3,6-bis[3-(ethoxycarbonyl)thioureido]acridine 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 ethyl N-[N'-[3-(dimethylamino)propyl]-N-[6-[[N'-[3-(dimethylamino)propyl]-N-ethoxycarbonylcarbamimidoyl]amino]acridin-3-yl]carbamimidoyl]carbamate
  参考文献：
  名称：

  Synthesis and evaluation of fused bispyrimidinoacridines as novel pentacyclic analogues of quadruplex-binder BRACO-19

  摘要：

  本文报道了一系列单嘧啶和双嘧啶吖啶的设计和合成，并评估了它们作为新型四联体结合剂的作用。结果表明，根据G4-FID检测和分子建模，双嘧啶吖啶在易于合成和四联体相互作用（亲和力和选择性）效率之间取得了有趣的平衡。本研究还强调，对配体与四联体DNA可及G四联体之间π堆积相互作用的控制对于良好识别确实至关重要，但并非唯一（直接和水介导的氢键的关键作用）。在吖啶系列中引入额外的氨基侧链，会导致配体/四联体识别的空间位阻，并降低四联体/双链的选择性。

  DOI：

  10.1039/b912716j

文献信息

• Synthesis of N-acridinyl-N′-alkylguanidines: Dramatic influence of amine to guanidine replacement on the physicochemical properties
  作者：Walid Zeghida、Julien Debray、Carine Michel、Anne Milet、Pascal Dumy、Martine Demeunynck

  DOI：10.1016/j.bmcl.2008.07.100

  日期：2008.9

  Transformation of aminoacridines into N-acridinyl-N'-alkylguanidines is described. The chosen procedure allows introduction of pendent substituents (exemplified by N,N-dimethylaminopropyl chain) into key acridinyl thioureas, thus opening the way to structural diversity. Spectroscopic study and pK(a) determination show that the presence of the strongly basic guanidine has a dramatic influence on the ionization of the acridine nucleus by lowering the pk(a) value down to 4.49. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of fused bispyrimidinoacridines as novel pentacyclic analogues of quadruplex-binder BRACO-19
  作者：Julien Debray、Walid Zeghida、Muriel Jourdan、David Monchaud、Marie-Louise Dheu-Andries、Pascal Dumy、Marie-Paule Teulade-Fichou、Martine Demeunynck

  DOI：10.1039/b912716j

  日期：——

  The present article reports on the design and the synthesis of a series of mono- and bis-pyrimidinoacridines and their evaluation as a novel family of quadruplex-binders. It is shown that bispyrimidinoacridines represent an interesting compromise between easy synthetic access and efficiency in terms of quadruplex interaction (both affinic and selective), as judged by G4-FID assay and molecular modelling. The present study also highlights that control of the π-stacking interactions taking place between the ligand and the accessible G-tetrad of a quadruplex-DNA is indeed essential for good recognition but not exclusively (key role of direct and water-mediated H-bonds). The introduction of additional amino side chains, valuable in the acridine series, results here in steric perturbations of the ligand/quadruplex recognition and lowers the quadruplex/duplex selectivity.

  本文报道了一系列单嘧啶和双嘧啶吖啶的设计和合成，并评估了它们作为新型四联体结合剂的作用。结果表明，根据G4-FID检测和分子建模，双嘧啶吖啶在易于合成和四联体相互作用（亲和力和选择性）效率之间取得了有趣的平衡。本研究还强调，对配体与四联体DNA可及G四联体之间π堆积相互作用的控制对于良好识别确实至关重要，但并非唯一（直接和水介导的氢键的关键作用）。在吖啶系列中引入额外的氨基侧链，会导致配体/四联体识别的空间位阻，并降低四联体/双链的选择性。