[N-(2-(2'-fluorophenyl)ethyl)glycyl]-[N-(3-methylbutyl)glycyl]-N-[3-(2'-oxopyrrolidinyl)propyl]glycinamide | 1268812-31-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [N-(2-(2'-fluorophenyl)ethyl)glycyl]-[N-(3-methylbutyl)glycyl]-N-[3-(2'-oxopyrrolidinyl)propyl]glycinamide
• 英文别名: N-[2-[(2-amino-2-oxoethyl)-[3-(2-oxopyrrolidin-1-yl)propyl]amino]-2-oxoethyl]-2-[2-(2-fluorophenyl)ethylamino]-N-(3-methylbutyl)acetamide
• CAS: 1268812-31-2
• 化学式: C₂₆H₄₀FN₅O₄
• 分子量: 505.633
• InChiKey: YOSRUTVSQOQUMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  36
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(3-氨基丙基)-2-吡咯烷酮 、 异戊胺 、 、 溴乙酸 、 2-氟苯乙胺 在 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.32h， 以56%的产率得到[N-(2-(2'-fluorophenyl)ethyl)glycyl]-[N-(3-methylbutyl)glycyl]-N-[3-(2'-oxopyrrolidinyl)propyl]glycinamide
  参考文献：
  名称：

  Peptoid agonists of nerve growth factor and their use as medicaments

  摘要：

  新的肽类神经生长因子激动剂及其用作药物。神经营养因子与其特定受体Trk A和p75结合，导致多个信号级联的激活，最终产生神经保护和再生效应，包括神经元存活和神经突起生长。神经营养因子已被用于治疗多种神经退行性疾病。然而，它们的使用受到其无法穿越血脑屏障、短半衰期和副作用的限制。小分子神经营养因子拟拟物可能有助于治疗多种神经退行性疾病。本发明显示了神经生长因子激动剂分子诱导PC12细胞分化、促进RN22细胞存活以及在这两种细胞系中以不同程度激活Trk A、IkBα和SAPK/JNK磷酸化的能力。此外，这些分子还能改善急性实验性自身免疫性脑脊髓炎（EAE），即多发性硬化（MS）动物模型，抑制脑部炎症并减少脑损伤。我们还观察到对诱导型一氧化氮合酶等促炎基因的产生有抑制作用。这些具有NGF激动剂活性的小分子可能由于其神经保护和免疫调节特性对MS和其他神经退行性疾病有益。

  公开号：

  EP2289886A1

文献信息

• Peptoid Agonists of Nerve Growth Factor and Their Use as Medicaments
  申请人：Moreno Beatriz

  公开号：US20120237552A1

  公开（公告）日：2012-09-20

  Neurotrophin binding to its specific receptors Trk A and p75 leads to the activation of multiple signalling cascades, culminating in neuroprotective and regenerative effects, including neuronal survival and neurite outgrowth. Neurotrophic factors have been used for the treatment of several neurodegenerative diseases. However, their use is limited by their inability to cross the blood-brain barrier, their short half life and their side effects. Small molecule neurotrophin mimetics may be beneficial in treating a number of neurodegenerative disorders. The present invention shows the capacity of nerve growth factor agonist molecules of Formulae I-IV, as defined in the specification, to induce differentiation in PC 12 cells, promote survival in RN22 cells and activate Trk A, IkBa and SAPK/JNK phosphorylation to various extents in both cell lines. In addition these molecules were able to ameliorate acute experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) animal model, inhibiting brain inflammation and reducing brain damage. We also observed suppression in the production of pro-inflammatory genes like the inducible nitric oxide synthase. These small molecules with NGF agonist activity may be beneficial for MS and other neurodegenerative diseases due to its neuroprotective and immunomodulatory properties.