2-(4-(1H-tetrazol-5-yl)phenyl)-1H-benzo[d]imidazole-4-carboxamide | 1196059-53-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(4-(1H-tetrazol-5-yl)phenyl)-1H-benzo[d]imidazole-4-carboxamide
• 英文别名: 2-[4-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazole-4-carboxamide
• CAS: 1196059-53-6
• 化学式: C₁₅H₁₁N₇O
• 分子量: 305.299
• InChiKey: HYLJXBLJEMWWFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  NU1092 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以58%的产率得到2-(4-(1H-tetrazol-5-yl)phenyl)-1H-benzo[d]imidazole-4-carboxamide
  参考文献：
  名称：

  Synthesis and Evaluation of a New Generation of Orally Efficacious Benzimidazole-Based Poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors as Anticancer Agents

  摘要：

  Small molecule inhibitors of PARP-1 have been pursued by various organizations as potential therapeutic agents either capable of sensitizing cytotoxic treatments or acting as stand-alone agents to combat cancer. As one of the strategies to expand our portfolio of PARP-1 inhibitors, we pursued unsaturated heterocycles to replace the saturated cyclic alpine derivatives appended to the benzimidazole core. Not only did a variety of these new generation compounds maintain high enzymatic potency, many of them also displayed robust cellular activity. For example, the enzymatic IC50 and cellular EC50 values were as low as 1 nM or below. Compounds 24 (EC50 = 3.7 nM) and 44 (EC50 = 7.8 nM), featuring an oxadiazole and a pyridine moiety, respectively, demonstrated balanced potency and PK profiles. In addition, these two molecules exhibited potent oral in vivo efficacy in potentiating the cytotoxic agent temozolomide in a B16F10 murine melanoma model.

  DOI：

  10.1021/jm900697r

文献信息

• Synthesis and Evaluation of a New Generation of Orally Efficacious Benzimidazole-Based Poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors as Anticancer Agents
  作者：Yunsong Tong、Jennifer J. Bouska、Paul A. Ellis、Eric F. Johnson、Joel Leverson、Xuesong Liu、Patrick A. Marcotte、Amanda M. Olson、Donald J. Osterling、Magdalena Przytulinska、Luis E. Rodriguez、Yan Shi、Nirupama Soni、Jason Stavropoulos、Sheela Thomas、Cherrie K. Donawho、David J. Frost、Yan Luo、Vincent L. Giranda、Thomas D. Penning

  DOI：10.1021/jm900697r

  日期：2009.11.12

  Small molecule inhibitors of PARP-1 have been pursued by various organizations as potential therapeutic agents either capable of sensitizing cytotoxic treatments or acting as stand-alone agents to combat cancer. As one of the strategies to expand our portfolio of PARP-1 inhibitors, we pursued unsaturated heterocycles to replace the saturated cyclic alpine derivatives appended to the benzimidazole core. Not only did a variety of these new generation compounds maintain high enzymatic potency, many of them also displayed robust cellular activity. For example, the enzymatic IC50 and cellular EC50 values were as low as 1 nM or below. Compounds 24 (EC50 = 3.7 nM) and 44 (EC50 = 7.8 nM), featuring an oxadiazole and a pyridine moiety, respectively, demonstrated balanced potency and PK profiles. In addition, these two molecules exhibited potent oral in vivo efficacy in potentiating the cytotoxic agent temozolomide in a B16F10 murine melanoma model.