4,8-diamino-1-benzyl-6H-6-iminoimidazo<4,5-e><1,3>diazepine | 162009-80-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑二氮卓类
• 英文名称: 4,8-diamino-1-benzyl-6H-6-iminoimidazo<4,5-e><1,3>diazepine
• 英文别名: 1-benzyl-4,8-diamino-6-imino-1,6-dihydroimidazo[4,5-e][1,3]diazepine；4,8-diamino-1-benzyl-6-iminoimidazo[4,5-e][1,3]diazepine；3-Benzyl-6-iminoimidazo[4,5-e][1,3]diazepine-4,8-diamine
• CAS: 162009-80-5
• 化学式: C₁₃H₁₃N₇
• 分子量: 267.293
• InChiKey: XVYUFUDNPUPIDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,8-diamino-1-benzyl-6H-6-iminoimidazo<4,5-e><1,3>diazepine 在 palladium dihydroxide 吡啶 、 bis(trimethylsilyl)trifluoroacetamide 、 三氟甲磺酸三甲基硅酯 、 氢气 作用下， 以 溶剂黄146 为溶剂， -45.0~25.0 ℃ 、275.79 kPa 条件下， 反应 26.0h， 生成 4,8-diamino-6-imino-6H-1-2',3',5'-tri-O-benzoyl-β-D-ribofuranosylimidazo[4,5-e][1,3]diazepine
  参考文献：
  名称：

  A Short Synthesis of a Novel Ring-Expanded Purine and Its Nucleoside Analogue Containing the Imidazo[4,5-e][1,3]diazepine Ring Skeleton with Multiple Amino Substituents Attached to the 7-Membered Ring

  摘要：

  The synthesis of 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine (1) and its nucleoside analogue (6) are reported. The heterocycle was prepared in a single step by condensation of 4,5-dicyanoimidazole with guanidine. The 5,7-fused ring structure of 1 was distinguished from the other possible 5:5-fused isomer 2 by preparing the N-15-labeled heterocycle (1*) and exploring its N-15-H-1 coupling patterns in both H-1 and N-15 NMR spectra. These spectral patterns also enabled establishment of the triamino tautomeric form of 1 as assigned. Compound 1, a novel ring-expanded (''fat'') analogue of purine, is anticipated to be planar and aromatic as predicted by molecular modeling. The 1-benzyl analogue (4), a protocol for the ribosyl analogue 6, was similarly prepared from 1-benzyl-4,5-dicyanoimidazole. The nucleoside 6 was prepared by the modified Vorbruggen ribosylation of 1. The position of ribosylation was unequivocally established by an unambiguous synthesis of 6 from condensation of 1-(2',3',5'-tri-O-benzoyl-beta-($) under bar D-ribofuranosyl)-4,5-dicyanoimidazole (7) with guanidine in a solution of sodium methoxide in methanol. The nucleoside 7 was prepared by the Vorbruggen ribosylation of 4,5-dicyanoimidazole.

  DOI：

  10.1080/15257779408013222
• 作为产物：
  描述：

  4,5-二氰基咪唑 在 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 4,8-diamino-1-benzyl-6H-6-iminoimidazo<4,5-e><1,3>diazepine
  参考文献：
  名称：

  含有5：7稠合的4,6,8-三氨基咪唑并[4,5- e ] [1,3]二氮杂ring环系统的化合物的合成，抗癌活性和SAR分析

  摘要：

  本文描述的是我们对5：7稠合杂环（1）的有限结构-活性关系（SAR）研究，该杂环包含4,6,8-三氨基咪唑并[4,5- e ] [1,3]二氮杂pine环系统，我们在几年前报道了其合成和有效的广谱抗癌活性。我们在这项研究中的SAR努力主要集中在杂环的N-1和N 6位上取代基的合法连接上。我们的结果表明，在杂环的N-1位上连接的取代基与在杂环的N 6位上连接的取代基之间存在一些微妙的相关性。在靶蛋白上可能有一个常见的疏水结合口袋，被N-1和N 6处的取代基所占据杂环配体的-位。该口袋似乎足够大，可以容纳N 6的C-18烷基链，而在N-1处没有任何连接，或者在N 6处具有结合的C-10，在N-1处具有CH 2 Ph。在N 6处短于或长于C-10且在N-1处连接有CH 2 Ph的任何烷基链会导致生物活性降低。

  DOI：

  10.1016/j.bmc.2016.03.015

文献信息

• Ring expanded nucleosides and nucleotides
  申请人：——

  公开号：US20040077564A1

  公开（公告）日：2004-04-22

  The present invention relates to compositions comprising analogues of purine nucleosides containing a ring-expanded (“fat”) heterocyclic ring, in place of purine, and an unmodified or modified sugar residue, pharmaceutically acceptable derivatives of such compositions, as well as methods of use thereof. In particular, these compositions may be utilized in the treatment of certain cancers, bacterial, fungal, parasitic, and viral infections, including, but not limited to, Acquired Immunodeficiency Syndrome (AIDS), hepatitis, Epstein-Barr and cytomegalovirus.

  本发明涉及含有环扩张（“肥胖”）杂环环代替嘌呤的嘌呤核苷类似物和未经改性或改性的糖残基的组合物，以及这些组合物的药学上可接受的衍生物，以及其使用方法。特别地，这些组合物可用于治疗某些癌症、细菌、真菌、寄生虫和病毒感染，包括但不限于获得性免疫缺陷综合症（AIDS）、肝炎、EB病毒和巨细胞病毒。
• Ring-expanded nucleosides and nucleotides
  申请人：Nabi

  公开号：EP1227103B1

  公开（公告）日：2006-07-26
• RING-EXPANDED NUCLEOSIDES AND NUCLEOTIDES
  申请人：Nabi

  公开号：EP0724587B1

  公开（公告）日：2002-09-04
• US6677310B1
  申请人：——

  公开号：US6677310B1

  公开（公告）日：2004-01-13
• A Short Synthesis of a Novel Ring-Expanded Purine and Its Nucleoside Analogue Containing the Imidazo[4,5-<i>e</i>][1,3]diazepine Ring Skeleton with Multiple Amino Substituents Attached to the 7-Membered Ring
  作者：L. Wang、A. Bhan、R. S. Hosmane、R. D. Guiles

  DOI：10.1080/15257779408013222

  日期：1994.12

  The synthesis of 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine (1) and its nucleoside analogue (6) are reported. The heterocycle was prepared in a single step by condensation of 4,5-dicyanoimidazole with guanidine. The 5,7-fused ring structure of 1 was distinguished from the other possible 5:5-fused isomer 2 by preparing the N-15-labeled heterocycle (1*) and exploring its N-15-H-1 coupling patterns in both H-1 and N-15 NMR spectra. These spectral patterns also enabled establishment of the triamino tautomeric form of 1 as assigned. Compound 1, a novel ring-expanded (''fat'') analogue of purine, is anticipated to be planar and aromatic as predicted by molecular modeling. The 1-benzyl analogue (4), a protocol for the ribosyl analogue 6, was similarly prepared from 1-benzyl-4,5-dicyanoimidazole. The nucleoside 6 was prepared by the modified Vorbruggen ribosylation of 1. The position of ribosylation was unequivocally established by an unambiguous synthesis of 6 from condensation of 1-(2',3',5'-tri-O-benzoyl-beta-($) under bar D-ribofuranosyl)-4,5-dicyanoimidazole (7) with guanidine in a solution of sodium methoxide in methanol. The nucleoside 7 was prepared by the Vorbruggen ribosylation of 4,5-dicyanoimidazole.