1-{2-amino-5-[({triisopropylsilyl}oxy)methyl]-1H-benzo[d]imidazol-1-yl}-2-methylpropan-2-ol | 1149753-39-8

• 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: 1-{2-amino-5-[({triisopropylsilyl}oxy)methyl]-1H-benzo[d]imidazol-1-yl}-2-methylpropan-2-ol
• 英文别名: 1-[2-Amino-5-[tri(propan-2-yl)silyloxymethyl]benzimidazol-1-yl]-2-methylpropan-2-ol
• CAS: 1149753-39-8
• 化学式: C₂₁H₃₇N₃O₂Si
• 分子量: 391.629
• InChiKey: LOSQEUIFFXQZIX-UHFFFAOYSA-N

物化性质

• 沸点：
  511.0±60.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  73.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(1H-吡唑-4-基)-2-噻吩羧酸 、 1-{2-amino-5-[({triisopropylsilyl}oxy)methyl]-1H-benzo[d]imidazol-1-yl}-2-methylpropan-2-ol 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 生成
  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
• 作为产物：
  描述：

  溴化氰 、 1-((2-amino-4-(((triisopropylsilyl)oxy)methyl)phenyl)amino)-2-methylpropan-2-ol 以 乙醇 为溶剂， 以88%的产率得到1-{2-amino-5-[({triisopropylsilyl}oxy)methyl]-1H-benzo[d]imidazol-1-yl}-2-methylpropan-2-ol
  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

• [EN] NOVEL UREA DERIVATIVES AS TEC KINASE INHIBITORS AND USES THEREOF<br/>[FR] NOUVEAUX DÉRIVÉS D'URÉE EN TANT QU'INHIBITEURS DE KINASE TEC ET LEURS UTILISATIONS
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2013024427A1

  公开（公告）日：2013-02-21

  Provided are urea compounds of formula (I) as Tec kinase inhibitors, in particular ITK (interleukin-2 inducible tyrosine kinase) inhibitors. Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders mediated by ITK.

  提供的是式（I）的尿素化合物，作为Tec激酶抑制剂，特别是ITK（白细胞介素-2诱导酪氨酸激酶）抑制剂。本文还提供了制备所述化合物的方法、用于合成的中间体、药物组合物以及治疗或预防由ITK介导的疾病、状况和/或紊乱的方法。