2-[4-(2-吡啶)苯基]-1H-苯并咪唑-7-羧酰胺 | 1196059-70-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 2-[4-(2-吡啶)苯基]-1H-苯并咪唑-7-羧酰胺
• 英文名称: 2-(4-(pyridin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide
• 英文别名: 2-(4-(pyridin-2-yl)phenyl)-1H-benzo[d]imidazole-4-carboxamide；2-(4-(piperidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide；1H-Benzimidazole-7-carboxamide, 2-[4-(2-pyridinyl)phenyl]-；2-(4-pyridin-2-ylphenyl)-1H-benzimidazole-4-carboxamide
• CAS: 1196059-70-7
• 化学式: C₁₉H₁₄N₄O
• 分子量: 314.346
• InChiKey: GTBYWKYWQWSPTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 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：
  84.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-[4-(2-吡啶)苯基]-1H-苯并咪唑-7-羧酰胺
  参考文献：
  名称：

  Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH

  摘要：

  Poly (ADP-ribose) polymerases (PARPs) play diverse roles in various cellular processes that involve DNA repair and programmed cell death. Amongst these polymerases is PARP-1 which is the key DNA damage-sensing enzyme that acts as an initiator for the DNA repair mechanism. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the pyrimidine biosynthetic pathway which is an important target for anti-hyperproliferative and anti-inflammatory drug design. Since these enzymes share a common role in the DNA replication and repair mechanisms, it may be beneficial to target both PARP-1 and DHODH in attempts to design new anti-cancer agents.Benzimidazole derivatives have shown a wide variety of pharmacological activities including PARP and DHODH inhibition. We hereby report the design, synthesis and bioactivities of a series of benzimidazole derivatives as inhibitors of both the PARP-1 and DHODH enzymes. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.051

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.
• Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH
  作者：Iskandar Abdullah、Chin Fei Chee、Yean-Kee Lee、Siva Sanjeeva Rao Thunuguntla、K. Satish Reddy、Kavitha Nellore、Thomas Antony、Jitender Verma、Kong Wai Mun、Shatrah Othman、Hosahalli Subramanya、Noorsaadah Abd. Rahman

  DOI：10.1016/j.bmc.2015.05.051

  日期：2015.8

  Poly (ADP-ribose) polymerases (PARPs) play diverse roles in various cellular processes that involve DNA repair and programmed cell death. Amongst these polymerases is PARP-1 which is the key DNA damage-sensing enzyme that acts as an initiator for the DNA repair mechanism. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the pyrimidine biosynthetic pathway which is an important target for anti-hyperproliferative and anti-inflammatory drug design. Since these enzymes share a common role in the DNA replication and repair mechanisms, it may be beneficial to target both PARP-1 and DHODH in attempts to design new anti-cancer agents.Benzimidazole derivatives have shown a wide variety of pharmacological activities including PARP and DHODH inhibition. We hereby report the design, synthesis and bioactivities of a series of benzimidazole derivatives as inhibitors of both the PARP-1 and DHODH enzymes. (C) 2015 Elsevier Ltd. All rights reserved.