3-(2-((4-甲脒基苯基)氨基)甲基)-1-甲基-N-(吡啶-2-基)-1H-苯并[d]咪唑-5-甲酰胺)丙酸乙酯 | 1188263-64-0

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 3-(2-((4-甲脒基苯基)氨基)甲基)-1-甲基-N-(吡啶-2-基)-1H-苯并[d]咪唑-5-甲酰胺)丙酸乙酯
• 英文名称: ethyl N-[(2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-(pyridin-2-yl)-β-alaninate bis(acetic acid salt)
• 英文别名: ethyl N-[(2-{[(4-carbamimidoylphenyl)-amino]methyl}-1-methyl-1H-benzimidazol-5-yl)-carbonyl]-N-pyridine-2-yl-β-alaninate acetic acid salt；Ethyl 3-(2-(((4-carbamimidoylphenyl)amino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate acetate；acetic acid;ethyl 3-[[2-[(4-carbamimidoylanilino)methyl]-1-methylbenzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoate
• CAS: 1188263-64-0
• 化学式: 2C₂H₄O₂*C₂₇H₂₉N₇O₃
• 分子量: 619.677
• InChiKey: UXDXRAAWSDVHMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  177
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-1,4-丁二胺 、 3-(2-((4-甲脒基苯基)氨基)甲基)-1-甲基-N-(吡啶-2-基)-1H-苯并[d]咪唑-5-甲酰胺)丙酸乙酯 以 乙醇 为溶剂， 反应 12.0h， 以91%的产率得到ethyl 3-(2-((4-(N-(4-(tert-butoxycarbonylamino)butyl)carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate
  参考文献：
  名称：

  Dabigatran and Dabigatran Ethyl Ester: Potent Inhibitors of Ribosyldihydronicotinamide Dehydrogenase (NQO2)

  摘要：

  Recent studies have revealed that compounds believed to be highly selective frequently address multiple target proteins. We investigated the protein interaction profile of the widely prescribed thrombin inhibitor dabigatran (1), resulting in the identification and subsequent characterization of an additional target enzyme. Our findings are based on an unbiased functional proteomics approach called capture compound mass spectrometry (CCMS) and were confirmed by independent biological assays. 1 was shown to specifically bind ribosyldihydronicotinamide dehydrogenase (NQO2), a detoxification oxidoreductase. Molecular dockings predicted and biological experiments confirmed that dabigatran ethyl ester (2) inhibits NQO2 even more effectively than the parent 1 itself. Our data show that 1 and 2 are inhibitors of NQO2, thereby revealing a possible new aspect in the mode of action of 1. We present a workflow employing chemical proteomics, molecular modeling, and functional assays by which a compound's protein-interaction profile can be determined and used to tune the binding affinity.

  DOI：

  10.1021/jm3001339
• 作为产物：
  描述：

  ethyl N-[4-(5-methyl-1,2,4-oxadiazole-3-yl)phenyl]glycinate 在 5%-palladium/activated carbon 、 1-丙基磷酸酐 、 sodium hydroxide 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 20.0~55.0 ℃ 、500.01 kPa 条件下， 反应 8.0h， 生成 3-(2-((4-甲脒基苯基)氨基)甲基)-1-甲基-N-(吡啶-2-基)-1H-苯并[d]咪唑-5-甲酰胺)丙酸乙酯
  参考文献：
  名称：

  PHARMACEUTICAL INTERMEDIATES AND PROCESS FOR THE PREPARATION THEREOF

  摘要：

  本发明涉及一种制备达比加群酯或其药用可接受盐的方法。

  公开号：

  US20140155614A1

文献信息

• [EN] PROCESS FOR THE MANUFACTURE OF DABIGATRAN ETEXILATE AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE FABRICATION D'ÉTÉXILATE DE DABIGATRAN ET DE SES INTERMÉDIAIRES
  申请人：EGIS GYOGYSZERGYAR NYILVANOSAN MUEKOEDOE RESZVENYTARSASAG

  公开号：WO2012153158A1

  公开（公告）日：2012-11-15

  The present invention relates to a process for the preparation of dabigatran etexilate of the formula (1) or the pharmaceutically accepted salts thereof.

  本发明涉及一种制备化合物达比加群酯（Dabigatran Etexilate）及其药用盐的方法。
• PHARMACEUTICAL INTERMEDIATES AND PROCESS FOR THE PREPARATION THEREOF
  申请人：Kiraly Imre

  公开号：US20140155614A1

  公开（公告）日：2014-06-05

  The present invention relates to a process for the preparation of dabigatran etexilate of the formula or pharmaceutically accepted salts thereof.

  本发明涉及一种制备达比加群酯或其药用可接受盐的方法。
• Dabigatran and Dabigatran Ethyl Ester: Potent Inhibitors of Ribosyldihydronicotinamide Dehydrogenase (NQO2)
  作者：Simon Michaelis、Anett Marais、Anna K. Schrey、Olivia Y. Graebner、Cornelia Schaudt、Michael Sefkow、Friedrich Kroll、Mathias Dreger、Mirko Glinski、Hubert Koester、Rainer Metternich、Jenny J. Fischer

  DOI：10.1021/jm3001339

  日期：2012.4.26

  Recent studies have revealed that compounds believed to be highly selective frequently address multiple target proteins. We investigated the protein interaction profile of the widely prescribed thrombin inhibitor dabigatran (1), resulting in the identification and subsequent characterization of an additional target enzyme. Our findings are based on an unbiased functional proteomics approach called capture compound mass spectrometry (CCMS) and were confirmed by independent biological assays. 1 was shown to specifically bind ribosyldihydronicotinamide dehydrogenase (NQO2), a detoxification oxidoreductase. Molecular dockings predicted and biological experiments confirmed that dabigatran ethyl ester (2) inhibits NQO2 even more effectively than the parent 1 itself. Our data show that 1 and 2 are inhibitors of NQO2, thereby revealing a possible new aspect in the mode of action of 1. We present a workflow employing chemical proteomics, molecular modeling, and functional assays by which a compound's protein-interaction profile can be determined and used to tune the binding affinity.