4-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-ylmethoxy)-3-methoxybenzaldehyde | 791591-62-3

• 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: 4-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-ylmethoxy)-3-methoxybenzaldehyde
• CAS: 791591-62-3
• 化学式: C₁₇H₂₂NO₄
• 分子量: 304.366
• InChiKey: YAWHSICKXMTLSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  39.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-ylmethoxy)-3-methoxybenzaldehyde 、 2,3-二氨基苯甲酰胺 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  New Poly(ADP-ribose) Polymerase-1 Inhibitors with Antioxidant Activity Based on 4-Carboxamidobenzimidazole-2-ylpyrroline and -tetrahydropyridine Nitroxides and Their Precursors

  摘要：

  4-Carboxamidobenzimidazoles were previously described as PARP inhibitor compounds. Here we report upon 4-carboxamido-1H-benzimidazoles substituted in the 2-position with nitroxides or their amine or hydroxylamine precursors. Among the new molecules, a highly active PARP inhibitor 4h (IC50 = 14 nM) was identified with antioxidant/radical scavenger activity. We concluded that in most cases sterically hindered amines are better PARP inhibitors than their oxidized form and structural changes in the 2-substituted 4-carboxamido-1H-benzimidazoles (such as N-substitution or changing the position of the carboxamide group) were detrimental to PARP inhibition activity but not to antioxidant activity. These results indicate the advantages of combining an antioxidant nitroxide or nitroxide precursor with a PARP inhibitor molecule to decrease or eliminate the deleterious processes initiated by reactive oxygen and reactive nitrogen species (ROS and RNS). The radical scavenging capability of 4h was demonstrated by EPR study of urine collected after drug administration.

  DOI：

  10.1021/jm801476y
• 作为产物：
  描述：

  3-(bromomethyl)-2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrol-1-oxyl 、 香草醛 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以88%的产率得到4-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-ylmethoxy)-3-methoxybenzaldehyde
  参考文献：
  名称：

  New Poly(ADP-ribose) Polymerase-1 Inhibitors with Antioxidant Activity Based on 4-Carboxamidobenzimidazole-2-ylpyrroline and -tetrahydropyridine Nitroxides and Their Precursors

  摘要：

  4-Carboxamidobenzimidazoles were previously described as PARP inhibitor compounds. Here we report upon 4-carboxamido-1H-benzimidazoles substituted in the 2-position with nitroxides or their amine or hydroxylamine precursors. Among the new molecules, a highly active PARP inhibitor 4h (IC50 = 14 nM) was identified with antioxidant/radical scavenger activity. We concluded that in most cases sterically hindered amines are better PARP inhibitors than their oxidized form and structural changes in the 2-substituted 4-carboxamido-1H-benzimidazoles (such as N-substitution or changing the position of the carboxamide group) were detrimental to PARP inhibition activity but not to antioxidant activity. These results indicate the advantages of combining an antioxidant nitroxide or nitroxide precursor with a PARP inhibitor molecule to decrease or eliminate the deleterious processes initiated by reactive oxygen and reactive nitrogen species (ROS and RNS). The radical scavenging capability of 4h was demonstrated by EPR study of urine collected after drug administration.

  DOI：

  10.1021/jm801476y

文献信息

• Synthesis and Biological Evaluation of Curcumin-Nitroxide-Based Molecular Hybrids as Antioxidant and Anti-Proliferative Agents
  作者：Balazs Bognar、M. Lakshmi Kuppusamy、Esha Madan、Tamas Kalai、Maria Balog、Jozsef Jeko、Periannan Kuppusamy、Kalman Hideg

  DOI：10.2174/1871520617666170522124712

  日期：2017.11.8

  incorporation of a nitroxide moiety or its precursor into curcumin or diarylidenylpiperidone (DAP) scaffolds resulted in anti-proliferative effect toward cancerous cell-lines in case of aryl hydroxy and/or methoxy substituent containing derivatives, suggesting their potential for targeted therapeutic applications. In case of basic side chain derivatives, nitroxide incorporation gave unambiguous results, however

  背景技术天然产物及其衍生物被广泛用于治疗与ROS和RNS诱导的损害有关的癌症和其他疾病。方法已设计，合成了一系列顺磁性修饰姜黄素类似物和3,5-二亚芳基哌啶酮（DAP），并具有抗增殖和抗氧化活性。结果新化合物的生物学特性支持了较早的结果，即在含有芳基羟基和/或甲氧基取代基的情况下，将氮氧化物部分或其前体掺入姜黄素或二芳基哌啶酮（DAP）支架中会导致对癌细胞系的抗增殖作用。衍生物，表明其潜在的靶向治疗应用。在碱性侧链衍生物的情况下，氮氧化物的引入产生了明确的结果，然而，趋向于更容易获得的DAP衍生物具有更强的抗增殖作用。在大多数情况下，氮氧化物的引入增加了DAP衍生物的TEAC值（质子和电子给体能力）。结论在合成和研究的化合物中，自旋标记的姜黄素和3,5-双（4-羟基-3-甲氧基亚苄基）哌啶-4-酮衍生物是最有效的抗增殖和抗氧化剂衍生物。