2-(1-cyclopentylpiperidin-4-yl)-1H-1,3-benzodiazole-4-carboxamide | 1062586-90-6

• 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-(1-cyclopentylpiperidin-4-yl)-1H-1,3-benzodiazole-4-carboxamide
• 英文别名: 2-(1-cyclopentylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide
• CAS: 1062586-90-6
• 化学式: C₁₈H₂₄N₄O
• 分子量: 312.415
• InChiKey: XAYSTJWGYXJQIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  75
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(4-piperidinyl)-1H-benzo[d]imidazole-4-carboxamide 、 环戊酮 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 2-(1-cyclopentylpiperidin-4-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

文献信息

• 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
  作者：Thomas D. Penning、Gui-Dong Zhu、Viraj B. Gandhi、Jianchun Gong、Sheela Thomas、Wilfried Lubisch、Roland Grandel、Wolfgang Wernet、Chang H. Park、Elizabeth H. Fry、Xuesong Liu、Yan Shi、Vered Klinghofer、Eric F. Johnson、Cherrie K. Donawho、David J. Frost、Velitchka Bontcheva-Diaz、Jennifer J. Bouska、Amanda M. Olson、Kennan C. Marsh、Yan Luo、Saul H. Rosenberg、Vincent L. Giranda

  DOI：10.1016/j.bmc.2008.05.044

  日期：2008.7

  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.