N,N'-(methylenedi-4,1-phenylene)bis[2-(1-pyrrolidinyl)acetamide] | 298215-35-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,N'-(methylenedi-4,1-phenylene)bis[2-(1-pyrrolidinyl)acetamide]
• 英文别名: GN8；2-pyrrolidin-1-yl-N-[4-[[4-[(2-pyrrolidin-1-ylacetyl)amino]phenyl]methyl]phenyl]acetamide
• CAS: 298215-35-7
• 化学式: C₂₅H₃₂N₄O₂
• 分子量: 420.555
• InChiKey: YNNKKMKHXXUFLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N'-(methylenedi-4,1-phenylene)bis[2-(1-pyrrolidinyl)acetamide] 在 lithium aluminium tetrahydride 、 Glauber's salt 作用下， 以 四氢呋喃 为溶剂， 反应 25.0h， 以91%的产率得到N,N'-bis[2-(1-pyrrolidinyl)ethyl]-4,4'-diaminodiphenylmethane
  参考文献：
  名称：

  Synthesis of GN8 derivatives and evaluation of their antiprion activity in TSE-infected cells

  摘要：

  A series of GN8 derivatives were synthesized from various diamines, carboxylic acid derivatives, and nitrogen nucleophiles, and their antiprion activity was tested in TSE-infected mouse neuronal cells. We found that two ethylenediamine units, hydrophobic substituents on the nitrogen atoms, and the diphenylmethane scaffold were essential structural features responsible for the activity. Seven derivatives bearing substituents at the benzylic position exhibited an improved antiprion activity with the IC50 values of 0.51-0.83 mu M. Conformational analysis of model compounds suggested that the introduction of the substituent at the benzylic position restricted the conformational variability of the diphenylmethane unit. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.132
• 作为产物：
  描述：

  4,4'-二氨基二苯甲烷 在 吡啶 、 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 N,N'-(methylenedi-4,1-phenylene)bis[2-(1-pyrrolidinyl)acetamide]
  参考文献：
  名称：

  Synthesis of GN8 derivatives and evaluation of their antiprion activity in TSE-infected cells

  摘要：

  A series of GN8 derivatives were synthesized from various diamines, carboxylic acid derivatives, and nitrogen nucleophiles, and their antiprion activity was tested in TSE-infected mouse neuronal cells. We found that two ethylenediamine units, hydrophobic substituents on the nitrogen atoms, and the diphenylmethane scaffold were essential structural features responsible for the activity. Seven derivatives bearing substituents at the benzylic position exhibited an improved antiprion activity with the IC50 values of 0.51-0.83 mu M. Conformational analysis of model compounds suggested that the introduction of the substituent at the benzylic position restricted the conformational variability of the diphenylmethane unit. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.132

文献信息

• Fluorimetric Detection of Insulin Misfolding by Probes Derived from Functionalized Fluorene Frameworks
  作者：Álvaro Sarabia-Vallejo、Ana Molina、Mónica Martínez-Orts、Alice D’Onofrio、Matteo Staderini、Maria Laura Bolognesi、M. Antonia Martín、Ana I. Olives、J. Carlos Menéndez

  DOI：10.3390/molecules29061196

  日期：——

  A group of functionalized fluorene derivatives that are structurally similar to the cellular prion protein ligand N,N′-(methylenedi-4,1-phenylene)bis [2-(1-pyrrolidinyl)acetamide] (GN8) have been synthesized. These compounds show remarkable native fluorescence due to the fluorene ring. The substituents introduced at positions 2 and 7 of the fluorene moiety are sufficiently flexible to accommodate the

  合成了一组结构与细胞朊病毒蛋白配体 N,N'-(亚甲基二-4,1-亚苯基)双[2-(1-吡咯烷基)乙酰胺] (GN8) 结构相似的功能化芴衍生物。由于芴环，这些化合物显示出显着的天然荧光。在芴部分的位置 2 和 7 处引入的取代基足够灵活，可以适应淀粉样蛋白中形成的 β 构象折叠。这些芴衍生物天然荧光的变化提供了胰岛素淀粉样蛋白聚集过程转变的证据。在存在天然胰岛素或淀粉样蛋白聚集体的情况下观察到的传感器荧光强度的增加表明它们有可能用作检测异常构象的荧光探针；因此，这些化合物可以用作“开启”荧光传感器。蛋白质-传感器解离常数在 5-10 μM 范围内，并且可以成功地利用蛋白质和传感器之间的分子间电荷转移过程来灵敏地检测异常胰岛素构象。由于传感器-蛋白质相互作用而获得的化合物 4 的 Stern-Volmer 猝灭常数值与参考化合物 GN8 获得的值相当。芴衍生物在清除活性氧（ROS）方面表现出良好的性能，并且根据
• NUCLEIC ACID COMPLEX
  申请人：Rena Therapeutics Inc.

  公开号：EP3366773A1

  公开（公告）日：2018-08-29

  [Problem to be Solved] Provided is a nucleic acid complex, preferably a double-stranded nucleic acid complex, having an excellent effect of suppressing the expression of a target gene. [Solution] The problem is solved by using a nucleic acid complex, preferably a double-stranded nucleic acid complex, comprising an active moiety comprising an antisense nucleic acid complementary to a transcript, for example, a transcript of a target gene, and a carrier moiety comprising a nucleic acid comprising DNA, preferably a DNA-based nucleic acid, which is complementary to the above-described nucleic acid.

  [有待解决的问题］ 本发明提供了一种核酸复合物，最好是一种双链核酸复合物，它在抑制目的基因的表达方面具有极佳的效果。 [解决方案］ 本发明通过使用一种核酸复合物（最好是双链核酸复合物）来解决上述问题，该核酸复合物由活性分子和载体分子组成，活性分子包括与转录物（例如目的基因的转录物）互补的反义核酸，载体分子包括与上述核酸互补的由 DNA（最好是 DNA 基核酸）组成的核酸。
• NUCLEIC ACID COMPLEX HAVING AT LEAST ONE BULGE STRUCTURE
  申请人：Rena Therapeutics Inc.

  公开号：EP3366774A1

  公开（公告）日：2018-08-29

  [Problem to be Solved] Provided is a nucleic acid complex, preferably a double-stranded nucleic acid complex, having an excellent effect of suppressing the expression of a target gene. [Solution] The problem is solved by using a nucleic acid complex, preferably a double-stranded nucleic acid complex, comprising an active moiety comprising an antisense nucleic acid complementary to a transcript, for example, a transcript of a target gene, and a carrier moiety comprising a nucleic acid complementary to the nucleic acid, and having at least one bulge structure.

  [有待解决的问题］ 本发明提供了一种核酸复合物，最好是一种双链核酸复合物，它在抑制目的基因的表达方面具有极佳的效果。 [解决方案］ 该问题是通过使用一种核酸复合物（最好是双链核酸复合物）来解决的，该核酸复合物包括一个活性分子，该活性分子由与转录本（例如目的基因的转录本）互补的反义核酸组成；以及一个载体分子，该载体分子由与该核酸互补的核酸组成，并具有至少一个隆起结构。
• Prion protein ligands as therapeutic agents for neurodegenerative disorders
  申请人：TRUSTEES OF BOSTON UNIVERSITY

  公开号：US10391068B2

  公开（公告）日：2019-08-27

  The invention provides compositions and methods for treatment of neurodegenerative diseases or disorders, particularly neurodegenerative diseases and disorders associated with protein aggregation. The present invention is based on the discovery of binding regions on the surface of PrPc, referred to as PrPc Binding Domains (PBD). In particular, the inventors have identified six different binding regions on PrPc, referred to herein as PrP-binding domain-1 (PBD-1), PrP-binding domain-2 (PBD-2), PrP-binding domain-3 (PBD-3), PrP-binding domain-4 (PBD-4), PrP-binding domain-5 (PBD-5), and PrP-binding domain-6 (PBD-6), herein. The PBD-1 to PBD-6 are each defined by a cluster of amino acids located in the globular domain of the protein, e.g., in the C-terminal half of the protein (i.e., in residues 120-230). One embodiment uses residues 127-226.

  本发明提供了治疗神经退行性疾病或紊乱的组合物和方法，特别是与蛋白质聚集相关的神经退行性疾病和紊乱。本发明基于 PrPc 表面结合区的发现，这些结合区被称为 PrPc 结合区（PBD）。特别是，本发明者在 PrPc 上发现了六个不同的结合区域，在此称为 PrP 结合域-1 (PBD-1)、PrP 结合域-2 (PBD-2)、PrP 结合域-3 (PBD-3)、PrP 结合域-4 (PBD-4)、PrP 结合域-5 (PBD-5) 和 PrP 结合域-6 (PBD-6)。PBD-1 至 PBD-6 分别由位于蛋白质球状结构域中的一组氨基酸定义，例如位于蛋白质的 C 端半部（即残基 120-230）。一个实施方案使用残基 127-226。
• JP2005120002A
  申请人：——

  公开号：JP2005120002A

  公开（公告）日：2005-05-12