N-(5-(aminomethyl)-1-(2-hydroxy-2-methylpropyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide | 1149753-47-8

• 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-(5-(aminomethyl)-1-(2-hydroxy-2-methylpropyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide
• 英文别名: N-[5-(aminomethyl)-1-(2-hydroxy-2-methylpropyl)benzimidazol-2-yl]-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide
• CAS: 1149753-47-8
• 化学式: C₂₀H₂₂N₆O₂S
• 分子量: 410.5
• InChiKey: ARDVVVHRXGYORG-UHFFFAOYSA-N

物化性质

• 密度：
  1.46±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  、 氨 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 生成 N-(5-(aminomethyl)-1-(2-hydroxy-2-methylpropyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide
  参考文献：
  名称：

  5-Aminomethylbenzimidazoles as potent ITK antagonists

  摘要：

  Benzamide 1 demonstrated good potency as a selective ITK inhibitor, however the amide moiety was found to be hydrolytically labile in vivo, resulting in low oral exposure and the generation of mutagenic aromatic amine metabolites. Replacing the benzamide with a benzylamine linker not only addressed the toxicity issue, but also improved the cellular and functional potency as well as the drug-like properties. SAR studies around the benzylamines and the identification of 10n and 10o as excellent tools for proof-of-concept studies are described. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.012

文献信息

• 5-Aminomethylbenzimidazoles as potent ITK antagonists
  作者：Doris Riether、Renée Zindell、Jennifer A. Kowalski、Brian N. Cook、Jörg Bentzien、Stéphane De Lombaert、David Thomson、Stanley Z. Kugler、Donna Skow、Leslie S. Martin、Ernest L. Raymond、Hnin Hnin Khine、Kathy O’Shea、Joseph R. Woska、Deborah Jeanfavre、Rosemarie Sellati、Kerry L.M. Ralph、Jennifer Ahlberg、Gabriel Labissiere、Mohammed A. Kashem、Steven S. Pullen、Hidenori Takahashi

  DOI：10.1016/j.bmcl.2009.02.012

  日期：2009.3

  Benzamide 1 demonstrated good potency as a selective ITK inhibitor, however the amide moiety was found to be hydrolytically labile in vivo, resulting in low oral exposure and the generation of mutagenic aromatic amine metabolites. Replacing the benzamide with a benzylamine linker not only addressed the toxicity issue, but also improved the cellular and functional potency as well as the drug-like properties. SAR studies around the benzylamines and the identification of 10n and 10o as excellent tools for proof-of-concept studies are described. (C) 2009 Elsevier Ltd. All rights reserved.