2-(4-bromophenyl)-1H-benzo[d]imidazole-4-carboxamide | 936551-58-5

• 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-bromophenyl)-1H-benzo[d]imidazole-4-carboxamide
• 英文别名: 2-(4-bromophenyl)-1H-benzimidazole-4-carboxamide
• CAS: 936551-58-5
• 化学式: C₁₄H₁₀BrN₃O
• 分子量: 316.157
• InChiKey: BALGSLRJXQZZFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-bromophenyl)-1H-benzo[d]imidazole-4-carboxamide 、 4-甲酰基苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 2-(4'-formylbipheny-4-yl)-1H-benzimidazole-4-carboxamide
  参考文献：
  名称：

  SUBSTITUTED 1H-BENZIMIDAZOLE-4-CARBOXAMIDES ARE POTENT PARP INHIBITORS

  摘要：

  化合物的化学式(I)抑制PARP酶，可用于治疗与PARP相关的疾病或疾病。还披露了包含化合物的药物组合物的化学式(I)，包含化合物的治疗方法的方法的化学式(I)，以及包含化合物的PARP酶抑制方法的方法的化学式(I)。

  公开号：

  US20070112047A1
• 作为产物：
  描述：

  2,3-二氨基苯甲酰胺二盐酸盐 、 对溴苯甲醛 在 钯 silica gel 、 methanol-dichloromethane 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以to provide the title compound (1.2 g, 17%)的产率得到2-(4-bromophenyl)-1H-benzo[d]imidazole-4-carboxamide
  参考文献：
  名称：

  Substituted 1H-benzimidazole-4-carboxamides are potent PARP inhibitors

  摘要：

  化合物(I)的公式可以抑制PARP酶并且对于治疗与PARP相关的疾病或疾病是有用的。同时还公开了包含化合物(I)的药物组合物，包括使用化合物(I)的治疗方法，以及使用化合物(I)抑制PARP酶的方法。

  公开号：

  US07462724B2

文献信息

• Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (<i>S</i>)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1<i>H</i>-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor
  作者：Thomas D. Penning、Gui-Dong Zhu、Jianchun Gong、Sheela Thomas、Viraj B. Gandhi、Xuesong Liu、Yan Shi、Vered Klinghofer、Eric F. Johnson、Chang H. Park、Elizabeth H. Fry、Cherrie K. Donawho、David J. Frost、Fritz G. Buchanan、Gail T. Bukofzer、Luis E. Rodriguez、Velitchka Bontcheva-Diaz、Jennifer J. Bouska、Donald J. Osterling、Amanda M. Olson、Kennan C. Marsh、Yan Luo、Vincent L. Giranda

  DOI：10.1021/jm901775y

  日期：2010.4.22

  We have developed a series of phenylpyrrolidine- and phenylpiperidine-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase (PARP) inhibitors with excellent PARP enzyme potency as well as single-digit nanomolar cellular potency. These efforts led to the identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (22b, A-966492). Compound 22b displayed excellent potency against the PARP-1 enzyme with a K-i of 1 nM and an EC50 of 1 nM in a whole cell assay. In addition, 22b is orally bioavailable across multiple species, crosses the blood brain barrier, and appears to distribute into tumor tissue. It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin.
• 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.
• US7462724B2
  申请人：——

  公开号：US7462724B2

  公开（公告）日：2008-12-09
• US7595406B2
  申请人：——

  公开号：US7595406B2

  公开（公告）日：2009-09-29
• [EN] SUBSTITUTED 1H-BENZIMIDAZOLE-4-CARBOXAMIDES ARE POTENT PARP INHIBITORS<br/>[FR] 1H-BENZIMIDAZOLE-4-CARBOXAMIDES SUBSTITUES EFFICACES EN TANT QU'INHIBITEURS DE PARP
  申请人：ABBOTT LAB

  公开号：WO2007059230A2

  公开（公告）日：2007-05-24

  [EN] Compounds of Formula (I) inhibit the PARP enzyme and are useful for treating a disease or a disorder associated with PARP. Also disclosed are pharmaceutical compositions comprising compounds of Formula (I), methods of treatment comprising compounds of Formula (I), and methods of inhibiting the PARP enzyme comprising compounds of Formula (I).
  [FR] L'invention concerne des composés répondant à la formule (I) inhibant l'enzyme PARP et utiles dans le traitement d'une pathologie ou d'un trouble associé à PARP. L'invention concerne également des compositions pharmaceutiques comprenant des composés répondant à la formule (I), des procédés de traitement comprenant des composés répondant à la formule (I) et des procédés d'inhibition de l'enzyme PARP comprenant des composés répondant à la formule (I).