1,3-Diydro-6-hydroxymethyl-1,1,3,3-tetramethyl-2H-pyrrolo[3,4-c]pyridin-2-yloxyl radical | 289913-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 1,3-Diydro-6-hydroxymethyl-1,1,3,3-tetramethyl-2H-pyrrolo[3,4-c]pyridin-2-yloxyl radical
• CAS: 289913-00-4
• 化学式: C₁₂H₁₇N₂O₂
• 分子量: 221.279
• InChiKey: ZJDDOKUWOMPODZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.71
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  56.26
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1,3-Diydro-6-hydroxymethyl-1,1,3,3-tetramethyl-2H-pyrrolo[3,4-c]pyridin-2-yloxyl radical 在 manganese(IV) oxide 作用下， 以 氯仿 为溶剂， 反应 2.0h， 以44%的产率得到2-oxyl-1,1,3,3-tetramethyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-6-carbaldehyde
  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：

  3,4-Bis(methylene)-2,2,5,5-tetramethylpyrrolidin-1-yloxyl radical 在 盐酸 、 氢氧化钾 、 sodium tetrahydroborate 、 sodium nitrite 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 26.67h， 生成 1,3-Diydro-6-hydroxymethyl-1,1,3,3-tetramethyl-2H-pyrrolo[3,4-c]pyridin-2-yloxyl radical
  参考文献：
  名称：

  Synthesis of Pyrroline Nitroxide Annulated Carbocycles and Heterocycles

  摘要：

  从对称型顺磁性二烯1开始，合成了吡咯啉硝基自由基融合的吡啶衍生物，如顺磁性奥美拉唑衍生物6、顺磁性醌类7b、8b、11，以及硝基自由基融合的吡咯14b和呋喃18。

  DOI：

  10.1055/s-2000-6280

文献信息

• New Poly(ADP-ribose) Polymerase-1 Inhibitors with Antioxidant Activity Based on 4-Carboxamidobenzimidazole-2-ylpyrroline and -tetrahydropyridine Nitroxides and Their Precursors
  作者：Tamás Kálai、Mária Balog、Alíz Szabó、Gergely Gulyás、József Jekő、Balázs Sümegi、Kálmán Hideg

  DOI：10.1021/jm801476y

  日期：2009.3.26

  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.
• Synthesis of Pyrroline Nitroxide Annulated Carbocycles and Heterocycles
  作者：Tamás Kálai、József Jekő、Kálmán Hideg

  DOI：10.1055/s-2000-6280

  日期：——

  Starting from symmetric paramagnetic diene 1, pyrroline nitroxide fused pyridine derivatives such as the paramagnetic omeprazole derivative 6, paramagnetic quinones 7b, 8b, 11, nitroxide fused pyrrole 14b and furan 18 were synthesized.

  从对称型顺磁性二烯1开始，合成了吡咯啉硝基自由基融合的吡啶衍生物，如顺磁性奥美拉唑衍生物6、顺磁性醌类7b、8b、11，以及硝基自由基融合的吡咯14b和呋喃18。