2-(1,1,3,3-tetramethyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-yl)-1H-benzimidazole-4-carboxylic acid amide | 1134350-13-2

• 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: 2-(1,1,3,3-tetramethyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-yl)-1H-benzimidazole-4-carboxylic acid amide
• 英文别名: 2-(1,1,3,3-tetramethyl-2H-pyrrolo[3,4-c]pyridin-6-yl)-1H-benzimidazole-4-carboxamide
• CAS: 1134350-13-2
• 化学式: C₁₉H₂₁N₅O
• 分子量: 335.409
• InChiKey: JHQFDFSYYLUONC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  96.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-oxyl-1,1,3,3-tetramethyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-6-carbaldehyde 、 2,3-二氨基苯甲酰胺 在 sodium metabisulfite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以55%的产率得到2-(1,1,3,3-tetramethyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-yl)-1H-benzimidazole-4-carboxylic acid amide
  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