6-Amino-9-benzyl-2-benzylamino-8-bromopurine | 226908-14-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-Amino-9-benzyl-2-benzylamino-8-bromopurine
• 英文别名: 6-Amino-9-benzyl-2-(n-benzylamino)-8-bromopurine；2-N,9-dibenzyl-8-bromopurine-2,6-diamine
• CAS: 226908-14-1
• 化学式: C₁₉H₁₇BrN₆
• 分子量: 409.288
• InChiKey: JUPKAKDZZMLEER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  81.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-Amino-9-benzyl-2-benzylamino-8-bromopurine 以 盐酸 为溶剂， 以23%的产率得到6-Amino-9-benzyl-2-benzylamino-8-hydroxypurine
  参考文献：
  名称：

  Heterocyclic compounds

  摘要：

  本发明涉及以下通式（I）的杂环化合物：其中X是硫原子、氧原子或—NR3—（R3可能通过氮原子与R1形成杂环环或取代杂环环），R1是烷基、取代烷基、芳基、取代芳基、杂环基或取代杂环基，R2是氢原子、卤原子等；或其药学上可接受的盐和干扰素诱导剂、抗病毒剂、抗癌剂和免疫性疾病治疗剂，包括化合物（I）或其药学上可接受的盐作为活性成分。

  公开号：

  US06329381B1
• 作为产物：
  描述：

  2-氯-6-氨基嘌呤 在 溴 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 6-Amino-9-benzyl-2-benzylamino-8-bromopurine
  参考文献：
  名称：

  Synthesis and structure–Activity relationships of 2-Amino-8-hydroxyadenines as orally active interferon inducing agents

  摘要：

  Recently, we have reported the 8-hydroxyadenine derivatives (2-4) as a novel class of interferon (IFN) inducing agents. In the present study, a series of 8-hydroxyadenines, which possess various amino moieties at the adenine C(2)-position, were synthesized and evaluated for their ability to induce endogenous IFN in comparison to the known active agent, Imiquimod. Among the compounds prepared, compound 9o possessing a 2-methoxyethylamino group at C(2)-position of adenine was found to exhibit potent IFN inducing activity in vivo. Compound 9o induced IFN from the dosage of 0.1 mg/kg, which was 30-fold potent than that of Imiquimod, and showed a good oral bioavailability (F = 81%) (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.032

文献信息

• Heterocyclic compounds
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：US06329381B1

  公开（公告）日：2001-12-11

  The present invention relates to a heterocyclic compound of the following general formula (I): wherein X is sulfur atom, oxygen atom or —NR3— (R3 may form a heterocyclic ring or a substituted heterocyclic ring with R1 via the nitrogen atom), R1 is alkyl group, substituted alkyl group, aryl group, substituted aryl group, heterocyclic group or substituted heterocyclic group, and R2 is hydrogen atom, halogen atom etc.; or its pharmaceutically acceptable salt and interferon inducers, antiviral agents, anticancer agents and therapeutic agents for immunologic diseases comprising the compound (I) or its pharmaceutically acceptable salt as active ingredients.

  本发明涉及以下通式（I）的杂环化合物：其中X是硫原子、氧原子或—NR3—（R3可能通过氮原子与R1形成杂环环或取代杂环环），R1是烷基、取代烷基、芳基、取代芳基、杂环基或取代杂环基，R2是氢原子、卤原子等；或其药学上可接受的盐和干扰素诱导剂、抗病毒剂、抗癌剂和免疫性疾病治疗剂，包括化合物（I）或其药学上可接受的盐作为活性成分。
• 8-Triazolylpurines: Towards Fluorescent Inhibitors of the MDM2/p53 Interaction
  作者：Mariell Pettersson、David Bliman、Jimmy Jacobsson、Jesper R. Nilsson、Jaeki Min、Luigi Iconaru、R. Kiplin Guy、Richard W. Kriwacki、Joakim Andréasson、Morten Grøtli

  DOI：10.1371/journal.pone.0124423

  日期：——

  Small molecule nonpeptidic mimics of α-helices are widely recognised as protein-protein interaction (PPIs) inhibitors. Protein-protein interactions mediate virtually all important regulatory pathways in a cell, and the ability to control and modulate PPIs is therefore of great significance to basic biology, where controlled disruption of protein networks is key to understanding network connectivity and function. We have designed and synthesised two series of 2,6,9-substituted 8-triazolylpurines as α-helix mimetics. The first series was designed based on low energy conformations but did not display any biological activity in a biochemical fluorescence polarisation assay targeting MDM2/p53. Although solution NMR conformation studies demonstrated that such molecules could mimic the topography of an α-helix, docking studies indicated that the same compounds were not optimal as inhibitors for the MDM2/p53 interaction. A new series of 8-triazolylpurines was designed based on a combination of docking studies and analysis of recently published inhibitors. The best compound displayed low micromolar inhibitory activity towards MDM2/p53 in a biochemical fluorescence polarisation assay. In order to evaluate the applicability of these compounds as biologically active and intrinsically fluorescent probes, their absorption/emission properties were measured. The compounds display fluorescent properties with quantum yields up to 50%.

  小分子非肽类α-螺旋模拟物被广泛认可为蛋白质-蛋白质相互作用（PPIs）的抑制剂。蛋白质-蛋白质相互作用几乎介导了细胞内所有重要的调控通路，因此控制和调节PPIs的能力对基础生物学具有重大意义，其中对蛋白质网络的可控破坏是理解网络连接和功能的关键。我们设计和合成了两系列2,6,9-取代的8-三唑基嘌呤作为α-螺旋模拟物。第一系列基于低能构象设计，但在针对MDM2/p53的生物化学荧光偏振分析中未显示出任何生物活性。尽管溶液NMR构象研究表明这些分子可以模拟α-螺旋的拓扑结构，但对接研究表明这些化合物作为MDM2/p53相互作用的抑制剂并不最优。基于对接研究和最近发表的抑制剂分析，设计了新的8-三唑基嘌呤系列。最佳化合物在生物化学荧光偏振分析中显示出对MDM2/p53的低微摩尔抑制活性。为了评估这些化合物作为具有内在荧光活性的探针的适用性，测量了它们的吸收/发射特性。这些化合物显示出高达50%的量子产率的荧光特性。
• NOVEL HETEROCYCLIC COMPOUNDS
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：EP1035123A1

  公开（公告）日：2000-09-13

  The present invention relates to a heterocyclic compound of the following general formula (I): wherein X is sulfur atom, oxygen atom or -NR3- (R3 may form a heterocyclic ring or a substituted heterocyclic ring with R1 via the nitrogen atom), R1 is alkyl group, substituted alkyl group, aryl group, substituted aryl group, heterocyclic group or substituted heterocyclic group, and R2 is hydrogen atom, halogen atom etc.; or its pharmaceutically acceptable salt and interferon inducers, antiviral agents, anticancer agents and therapeutic agents for immunologic diseases comprising the compound (I) or its pharmaceutically acceptable salt as active ingredients.

  本发明涉及以下通式(I)的杂环化合物： 其中 X 是硫原子、氧原子或-NR3-（R3 可通过氮原子与 R1 形成杂环或取代的杂环）、 R1 是烷基、取代的烷基、芳基、取代的芳基、杂环基或取代的杂环基，以及 R2 是氢原子、卤素原子等； 或其药学上可接受的盐，以及干扰素诱导剂、抗病毒剂、抗癌剂和以化合物（I）或其药学上可接受的盐为活性成分的免疫疾病治疗剂。
• US6329381B1
  申请人：——

  公开号：US6329381B1

  公开（公告）日：2001-12-11
• Synthesis and structure–Activity relationships of 2-Amino-8-hydroxyadenines as orally active interferon inducing agents
  作者：Ayumu Kurimoto、Tetsuhiro Ogino、Shinji Ichii、Yoshiaki Isobe、Masanori Tobe、Haruhisa Ogita、Haruo Takaku、Hironao Sajiki、Kosaku Hirota、Hajime Kawakami

  DOI：10.1016/j.bmc.2003.09.032

  日期：2003.12

  Recently, we have reported the 8-hydroxyadenine derivatives (2-4) as a novel class of interferon (IFN) inducing agents. In the present study, a series of 8-hydroxyadenines, which possess various amino moieties at the adenine C(2)-position, were synthesized and evaluated for their ability to induce endogenous IFN in comparison to the known active agent, Imiquimod. Among the compounds prepared, compound 9o possessing a 2-methoxyethylamino group at C(2)-position of adenine was found to exhibit potent IFN inducing activity in vivo. Compound 9o induced IFN from the dosage of 0.1 mg/kg, which was 30-fold potent than that of Imiquimod, and showed a good oral bioavailability (F = 81%) (C) 2003 Elsevier Ltd. All rights reserved.