2-[piperidin-2-yl]-1H-benzimidazole-4-carboxamide | 944417-88-3

• 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-[piperidin-2-yl]-1H-benzimidazole-4-carboxamide
• 英文别名: 2-(piperidin-2-yl)-1H-1,3-benzodiazole-4-carboxamide；2-piperidin-2-yl-1H-benzimidazole-4-carboxamide
• CAS: 944417-88-3
• 化学式: C₁₃H₁₆N₄O
• 分子量: 244.296
• InChiKey: QRGBDUGNPYKQHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[piperidin-2-yl]-1H-benzimidazole-4-carboxamide 、 聚合甲醛 在 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 生成 2-(1-methylpiperidin-2-yl)-1H-1,3-benzodiazole-4-carboxamide
  参考文献：
  名称：

  Discovery and SAR of 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer

  摘要：

  We have developed a series of cyclic amine-containing benzimidazole carboxamide poly( ADPribose) polymerase ( PARP) inhibitors, with good PARP-1 enzyme potency, as well as cellular potency. These efforts led to the identification of a lead preclinical candidate, 10b, 2-(1-propylpiperidin-4-yl)-1H-benzimidazole- 4-carboxamide (A-620223). 10b displayed very good potency against both the PARP-1 enzyme with a K-i of 8 nM and in a whole cell assay with an EC50 of 3 nM. 10b is aqueous soluble, orally bioavailable across multiple species, and demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide ( TMZ) and in an MX-1 breast xenograph model in combination with cisplatin. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.044
• 作为产物：
  描述：

  在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 2-[piperidin-2-yl]-1H-benzimidazole-4-carboxamide
  参考文献：
  名称：

  Discovery and SAR of 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer

  摘要：

  We have developed a series of cyclic amine-containing benzimidazole carboxamide poly( ADPribose) polymerase ( PARP) inhibitors, with good PARP-1 enzyme potency, as well as cellular potency. These efforts led to the identification of a lead preclinical candidate, 10b, 2-(1-propylpiperidin-4-yl)-1H-benzimidazole- 4-carboxamide (A-620223). 10b displayed very good potency against both the PARP-1 enzyme with a K-i of 8 nM and in a whole cell assay with an EC50 of 3 nM. 10b is aqueous soluble, orally bioavailable across multiple species, and demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide ( TMZ) and in an MX-1 breast xenograph model in combination with cisplatin. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.044

文献信息

• 1H-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position are potent PARP inhibitors
  申请人：Zhu Gui-Dong

  公开号：US20060229289A1

  公开（公告）日：2006-10-12

  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).

  公式(I)的化合物抑制PARP酶，并且对于治疗与PARP相关的疾病或障碍是有用的。还披露了包括公式(I)化合物的药物组合物、包括公式(I)化合物的治疗方法，以及包括公式(I)化合物的抑制PARP酶的方法。
• Combination therapy with PARP inhibitors
  申请人：Abbott Laboratories

  公开号：EP2329818A1

  公开（公告）日：2011-06-08

  The present invention describes benzimidazole derivatives of Formula (I) which constitute potent PARP inhibitors in combination with other chemotherapeutic agents..

  本发明描述了式(I)的苯并咪唑衍生物，这些衍生物与其他化疗药物联合使用可构成强效的PARP抑制剂。
• 1H-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position as PARP inhibitors for use in treating cancer
  申请人：Abbott Laboratories

  公开号：EP2420234A1

  公开（公告）日：2012-02-22

  Compounds of Formula (I) (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).

  式(I)(I)化合物抑制PARP酶，可用于治疗与PARP相关的疾病或紊乱。还公开了包含式（I）化合物的药物组合物、包含式（I）化合物的治疗方法以及包含式（I）化合物的抑制 PARP 酶的方法。
• 1H-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position as potent PARP inhibitors
  申请人：Abbott Laboratories

  公开号：EP2420499A1

  公开（公告）日：2012-02-22

  Compounds of Formula (I) (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).

  式(I)(I)化合物抑制PARP酶，可用于治疗与PARP相关的疾病或紊乱。还公开了包含式（I）化合物的药物组合物、包含式（I）化合物的治疗方法以及包含式（I）化合物的抑制 PARP 酶的方法。
• 1H-BENZIMIDAZOLE-4-CARBOXAMIDES SUBSTITUTED WITH A QUATERNARY CARBON AT THE 2-POSITION ARE POTENT PARP INHIBITORS
  申请人：Abbott Laboratories

  公开号：EP1869011B1

  公开（公告）日：2012-08-01