N-[[1-[2-hydroxy-3-(methylamino)propyl]piperidin-4-yl]methyl]-2-propan-2-yl-1H-benzimidazole-4-carboxamide | 1446251-08-6

• 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: N-[[1-[2-hydroxy-3-(methylamino)propyl]piperidin-4-yl]methyl]-2-propan-2-yl-1H-benzimidazole-4-carboxamide
• CAS: 1446251-08-6
• 化学式: C₂₁H₃₃N₅O₂
• 分子量: 387.525
• InChiKey: VCGGCROJRORJQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  93.3
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[[1-[2-hydroxy-3-(methylamino)propyl]piperidin-4-yl]methyl]-2-propan-2-yl-1H-benzimidazole-4-carboxamide 、 乙酰氯 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[[1-[3-[acetyl(methyl)amino]-2-hydroxypropyl]piperidin-4-yl]methyl]-2-propan-2-yl-1H-benzimidazole-4-carboxamide
  参考文献：
  名称：

  Discovery of TD-8954, a clinical stage 5-HT4 receptor agonist with gastrointestinal prokinetic properties

  摘要：

  The discovery of a series of 5-HT4 receptor agonists based on a novel 2-alkylbenzimidazole aromatic core is described. Optimization of the 2-substituent of the benzimidazole ring led to a series of agonists with subnanomolar binding affinity and moderate-to-high intrinsic activity relative to that of 5-HT. Consistent with our previously described multivalent design approach to this target, subsequent optimization of the linker and secondary binding group regions of the series afforded compound 18 (TD-8954), a potent and selective 5-HT4 receptor agonist in vitro with demonstrated prokinetic activity in multiple species. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.018
• 作为产物：
  描述：

  2-isopropyl-N-(piperidin-4-ylmethyl)-1H-benzo[d]imidazole-4-carboxamide 以 乙醇 为溶剂， 生成 N-[[1-[2-hydroxy-3-(methylamino)propyl]piperidin-4-yl]methyl]-2-propan-2-yl-1H-benzimidazole-4-carboxamide
  参考文献：
  名称：

  Discovery of TD-8954, a clinical stage 5-HT4 receptor agonist with gastrointestinal prokinetic properties

  摘要：

  The discovery of a series of 5-HT4 receptor agonists based on a novel 2-alkylbenzimidazole aromatic core is described. Optimization of the 2-substituent of the benzimidazole ring led to a series of agonists with subnanomolar binding affinity and moderate-to-high intrinsic activity relative to that of 5-HT. Consistent with our previously described multivalent design approach to this target, subsequent optimization of the linker and secondary binding group regions of the series afforded compound 18 (TD-8954), a potent and selective 5-HT4 receptor agonist in vitro with demonstrated prokinetic activity in multiple species. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.018

文献信息

• Discovery of TD-8954, a clinical stage 5-HT4 receptor agonist with gastrointestinal prokinetic properties
  作者：R. Murray McKinnell、Scott R. Armstrong、David T. Beattie、Paul R. Fatheree、Daniel D. Long、Daniel G. Marquess、Jeng-Pyng Shaw、Ross G. Vickery

  DOI：10.1016/j.bmcl.2013.05.018

  日期：2013.7

  The discovery of a series of 5-HT4 receptor agonists based on a novel 2-alkylbenzimidazole aromatic core is described. Optimization of the 2-substituent of the benzimidazole ring led to a series of agonists with subnanomolar binding affinity and moderate-to-high intrinsic activity relative to that of 5-HT. Consistent with our previously described multivalent design approach to this target, subsequent optimization of the linker and secondary binding group regions of the series afforded compound 18 (TD-8954), a potent and selective 5-HT4 receptor agonist in vitro with demonstrated prokinetic activity in multiple species. (C) 2013 Elsevier Ltd. All rights reserved.