2-[3-(cyclopentylamino)-1-methylpropyl]-1H-benzimidazole-4-carboxamide | 912335-95-6

• 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-[3-(cyclopentylamino)-1-methylpropyl]-1H-benzimidazole-4-carboxamide
• 英文别名: 2-(4-(cyclopentylamino)butan-2-yl)-1H-benzo[d]imidazole-4-carboxamide；2-[4-(cyclopentylamino)butan-2-yl]-1H-benzimidazole-4-carboxamide
• CAS: 912335-95-6
• 化学式: C₁₇H₂₄N₄O
• 分子量: 300.404
• InChiKey: NPMJSVQNMVYLOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(3-amino-1-methylpropyl)-1H-benzimidazole-4-carboxamide 、 环戊酮 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 生成 2-[3-(cyclopentylamino)-1-methylpropyl]-1H-benzimidazole-4-carboxamide
  参考文献：
  名称：

  具有季亚甲基-氨基取代基的聚（ADP-核糖）聚合酶（PARP）的新颖，有效且可口服生物利用的苯并咪唑抑制剂的合成和SAR。

  摘要：

  聚（ADP-核糖）聚合酶（PARP）在各种细胞功能（包括DNA修复和RNA转录控制）中起重要作用。在许多动物肿瘤模型中，PARP抑制剂已被证明可增强细胞毒剂或放射的作用。利用其中苯甲酰胺形成关键的分子内氢键以与酶进行最佳相互作用的苯并咪唑羧酰胺支架，我们确定了一系列新型的PARP抑制剂，在苯并咪唑的C-2位上含有季亚甲基-氨基取代基。在固有和细胞分析中，亚甲基-氨基取代基上的双甲基二甲基类似物通常比单甲基衍生物更有效。较小的环烷烃（例如环丙基或环丁基）在季碳原子上具有耐受性，而较大的环则不利于效能。针对两个优化的类似物，描述了B16F10小鼠侧腹黑色素瘤模型与替莫唑胺（TMZ）结合的体内功效数据。

  DOI：

  10.1016/j.bmcl.2008.06.023

文献信息

• 2-Substituted-1 H-benzimidazile-4-carboxamides are PARP inhibitors
  申请人：Zhu Gui-Dong

  公开号：US20060229351A1

  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), method of treatment comprising compounds of Formula (I), and methods of inhibiting the PARP enzyme comprising compound of Formula (I).

  公式（I）的化合物抑制PARP酶，可用于治疗与PARP相关的疾病或紊乱。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。
• 2-SUBSTITUTED-1H-BENZIMIDAZOLE-4-CARBOXAMIDES ARE PARP INHIBITORS
  申请人：Zhu Gui-Dong

  公开号：US20100234425A1

  公开（公告）日：2010-09-16

  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）的化合物能够抑制PARP酶，适用于治疗与PARP相关的疾病或疾病。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PARP酶抑制方法。
• USE OF DIANHYDROGALACTITOL OR DERIVATIVES OR ANALOGS THEREOF FOR TREATMENT OF PEDIATRIC CENTRAL NERVOUS SYSTEM MALIGNANCIES
  申请人：DelMar Pharmaceuticals, Inc.

  公开号：US20180071244A1

  公开（公告）日：2018-03-15

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of malignancies of the central nervous system in pediatric patients, including glioblastoma multiforme (GBM) high grade glioma, and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N 7 methylation and that can induce double-stranded breaks in DNA. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents (e.g. cisplatin) and can possess additive or super-additive effects.
• USE OF DIANHYDROGALACTITOL AND DERIVATIVES THEREOF IN THE TREATMENT OF GLIOBLASTOMA, LUNG CANCER, AND OVARIAN CANCER
  申请人：Bacha Jeffrey A.

  公开号：US20190091195A1

  公开（公告）日：2019-03-28

  Substituted hexitol derivatives such as dianhydrogalactitol are useful in the treatment of various neoplastic pathologies. Said pathologies include glioblastoma multiforme, non-small-cell lung carcinoma (NSCLC), ovarian cancer, and leptomeningeal carcinomatosis. The anti-neoplastic activity of dianhydrogalactitol is demonstrated to be due to its activity as an alkylating agent that creates N 7 methylation and inter-strand DNA crosslinks. The hexitol derivatives may be used alone or in combination with other anti-neoplastic agents.
• US7728026B2
  申请人：——

  公开号：US7728026B2

  公开（公告）日：2010-06-01