2-[4-(3-Diethylcarbamoyl-phenoxy)-phenyl]-1H-benzoimidazole-5-carboxylic Acid Amide

• 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-(3-Diethylcarbamoyl-phenoxy)-phenyl]-1H-benzoimidazole-5-carboxylic Acid Amide
• 英文别名: 2-[4-[3-(diethylcarbamoyl)phenoxy]phenyl]-3H-benzimidazole-5-carboxamide
• 化学式: C₂₅H₂₄N₄O₃
• 分子量: 428.491
• InChiKey: YOVVTBDGHWCNBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  间羟基苯甲酸 在 sodium metabisulfite 、 1-羟基苯并三唑 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 2-[4-(3-Diethylcarbamoyl-phenoxy)-phenyl]-1H-benzoimidazole-5-carboxylic Acid Amide
  参考文献：
  名称：

  Checkpoint Kinase Inhibitors:  SAR and Radioprotective Properties of a Series of 2-Arylbenzimidazoles

  摘要：

  The discovery of a series of novel, potent, and highly selective inhibitors of the DNA damage control kinase chk2 is disclosed. Here we report the first SAR study around inhibitors of this kinase. High-throughput screening of purified human chk2 led to the identification of a novel series of 2-arylbenzimidazole inhibitors of the kinase. Optimization was facilitated using homology models of chk2 and docking of inhibitors, leading to the highly potent 2-arylbenzimidazole 2h (IC50 15 nM). Compound 2h is an ATP-competitive inhibitor of chk2 that dose dependently protects human CD4+ and CD8+ T-cells from apoptosis due to ionizing radiation. This work suggests that a selective small molecule inhibitor of chk2 could be a useful adjuvant to radiotherapy, increasing the therapeutic window of such treatment.

  DOI：

  10.1021/jm0495935

文献信息

• Methods for Chk2 inhibitor patient selection
  申请人：Altieri Dario

  公开号：US20080125358A1

  公开（公告）日：2008-05-29

  The present invention contemplates a method to identify subjects that either have a tumor, or are at risk for tumor development, that are responsive to various inhibitors of an activated-Chk2 protein. Such Chk2 inhibitors may comprise a benzimidazole core structure, and derivatives thereof. Other Chk2 inhibitors may comprise nucleic acids, such as silencing interference RNA's specific for a Chk2 expression. Other Chk2 inhibitors may comprises proteins, such as antibodies. For example, the present invention contemplates that when a Chk2 inhibitor is administered during, or after, ionizing radiation tumor cell apoptosis is increased.

  本发明考虑了一种用于识别患有肿瘤或患有肿瘤风险、对激活的Chk2蛋白的各种抑制剂具有响应的受试者的方法。这些Chk2抑制剂可能包括苯并咪唑核结构及其衍生物。其他Chk2抑制剂可能包括核酸，例如特异于Chk2表达的沉默干扰RNA。其他Chk2抑制剂可能包括蛋白质，例如抗体。例如，本发明考虑了当在电离辐射期间或之后给予Chk2抑制剂时，肿瘤细胞凋亡增加。
• Substituted benzimidazoles and imidazo-[4,5]-pyridines
  申请人：——

  公开号：US20030176438A1

  公开（公告）日：2003-09-18

  2-Aryl substituted benzimidazoles and imidazo[4,5]pyridines are disclosed as inhibitors of Cds 1 and useful as adjuvants to chemotherapy or radiation therapy in the treatment of cancer.

  2-芳基取代苯并咪唑和咪唑[4,5]吡啶被披露为Cds1的抑制剂，并在癌症治疗中作为化疗或放疗的辅助剂。
• Substituted Benzimidazoles and Imidazo-[4,5]-Pyridines
  申请人：Arienti L. Kristen

  公开号：US20080009493A1

  公开（公告）日：2008-01-10

  2-Aryl substituted benzimidazoles and imidazo[4,5]pyridines are disclosed as inhibitors of Cds1 and useful as adjuvants to chemotherapy or radiation therapy in the treatment of cancer.

  2-芳基取代苯并咪唑和咪唑[4,5]吡啶被披露为Cds1的抑制剂，并可用作辅助化疗或放疗治疗癌症。
• 2-PHENYL BENZIMIDAZOLES AND IMIDAZO-¬4,5|-PYRIDINES AS CDS1/CHK2-INHIBITORS AND ADJUVANTS TO CHEMOTHERAPY OR RADIATION THERAPY IN THE TREATMENT OF CANCER
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1435947B1

  公开（公告）日：2007-08-15
• 2-PHENYL BENZIMIDAZOLES AND IMIDAZO-[4,5]-PYRIDINES AS CDS1/CHK2-INHIBITORS AND ADJUVANTS TO CHEMOTHERAPY OR RADIATION THERAPY IN THE TREATMENT OF CANCER
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1435947A1

  公开（公告）日：2004-07-14