2-isopropyl-1H-benzoimidazole-4-carboxylic acid (1-piperidin-4-ylmethylpiperidin-4-ylmethyl)amide | 916076-06-7

• 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-isopropyl-1H-benzoimidazole-4-carboxylic acid (1-piperidin-4-ylmethylpiperidin-4-ylmethyl)amide
• 英文别名: N-[[1-(piperidin-4-ylmethyl)piperidin-4-yl]methyl]-2-propan-2-yl-1H-benzimidazole-4-carboxamide
• CAS: 916076-06-7
• 化学式: C₂₃H₃₅N₅O
• 分子量: 397.564
• InChiKey: DUXVJGFBMZVLAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  73
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-isopropyl-1H-benzoimidazole-4-carboxylic acid (1-piperidin-4-ylmethylpiperidin-4-ylmethyl)amide 、 氯甲酸苯酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以24%的产率得到4-(4-{[(2-isopropyl-1H-benzoimidazole-4-carbonyl)-amino]-methyl}piperidin-1-ylmethyl)piperidine-1-carboxylic acid phenyl ester bis-trifluoroacetate
  参考文献：
  名称：

  Benzimidazole-carboxamide compounds as 5-HT4, receptor agonists

  摘要：

  这项发明涉及式(I)的苯并咪唑-羧酰胺5-HT4受体激动剂化合物，其中R1和X如规范中定义，或其药学上可接受的盐、溶剂合物或立体异构体。该发明还涉及包含这种化合物的药物组合物，使用这种化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这种化合物的过程和中间体。

  公开号：

  US20060270652A1
• 作为产物：
  描述：

  2-isopropyl-N-(piperidin-4-ylmethyl)-1H-benzo[d]imidazole-4-carboxamide 在 三乙酰氧基硼氢化钠 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-isopropyl-1H-benzoimidazole-4-carboxylic acid (1-piperidin-4-ylmethylpiperidin-4-ylmethyl)amide
  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

• BENZIMIDAZOLE-CARBOXAMIDE COMPOUNDS AS 5-HT4 RECEPTOR AGONISTS
  申请人：McKinnell Robert Murray

  公开号：US20100249186A1

  公开（公告）日：2010-09-30

  The invention relates to benzimidazole-carboxamide 5-HT 4 receptor agonist compounds of formula (I) wherein R 1 and X are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention also relates to pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT 4 receptor activity, and processes and intermediates useful for preparing such compounds.

  本发明涉及一种苯并咪唑-羧酰胺5-HT4受体激动剂化合物，其化学式为(I)，其中R1和X如规范中所定义，或其药学上可接受的盐、溶剂或立体异构体。本发明还涉及包含这种化合物的制药组合物，使用这种化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这种化合物的过程和中间体。
• Benzimidazole-carboxamide compounds as 5-HT4 receptor agonists
  申请人：Theravance, Inc.

  公开号：US08143279B2

  公开（公告）日：2012-03-27

  The invention relates to benzimidazole-carboxamide 5-HT4 receptor agonist compounds of formula (I) wherein R1 and X are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention also relates to pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT4 receptor activity, and processes and intermediates useful for preparing such compounds. The invention further relates to crystalline forms of a compound of formula (I).

  本发明涉及式(I)的苯并咪唑-羧酰胺5-HT4受体激动剂化合物，其中R1和X如规范所定义，或其药学上可接受的盐或溶剂或立体异构体。本发明还涉及包含这些化合物的制药组合物，使用这些化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这些化合物的过程和中间体。本发明还涉及式(I)化合物的晶体形式。
• Benzimidazole-carboxamide compounds as 5-ht4 receptor agonists
  申请人：McKinnell Robert Murray

  公开号：US20090209582A1

  公开（公告）日：2009-08-20

  The invention relates to benzimidazole-carboxamide 5-HT 4 receptor agonist compounds of formula (I) wherein R 1 and X are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention also relates to pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT 4 receptor activity, and processes and intermediates useful for preparing such compounds. The invention further relates to crystalline forms of a compound of formula (I).

  本发明涉及公式（I）中的苯并咪唑-羧酰胺5-HT4受体激动剂化合物，其中R1和X如规范中所定义，或其药学上可接受的盐或溶剂或立体异构体。本发明还涉及包括这些化合物的制药组合物，使用这些化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这些化合物的过程和中间体。本发明还涉及公式（I）化合物的晶体形式。
• US8143279B2
  申请人：——

  公开号：US8143279B2

  公开（公告）日：2012-03-27
• Benzimidazole-carboxamide compounds as 5-HT4, receptor agonists
  申请人：McKinnell Murray Robert

  公开号：US20060270652A1

  公开（公告）日：2006-11-30

  The invention relates to benzimidazole-carboxamide 5-HT 4 receptor agonist compounds of formula (I) wherein R 1 and X are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention also relates to pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with 5-HT 4 receptor activity, and processes and intermediates useful for preparing such compounds.

  这项发明涉及式(I)的苯并咪唑-羧酰胺5-HT4受体激动剂化合物，其中R1和X如规范中定义，或其药学上可接受的盐、溶剂合物或立体异构体。该发明还涉及包含这种化合物的药物组合物，使用这种化合物治疗与5-HT4受体活性相关的疾病的方法，以及用于制备这种化合物的过程和中间体。