N-[1-(3-amino-3-oxopropyl)-5-[benzoyl(methyl)amino]benzimidazol-2-yl]thiophene-2-carboxamide | 1085938-58-4

• 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-(3-amino-3-oxopropyl)-5-[benzoyl(methyl)amino]benzimidazol-2-yl]thiophene-2-carboxamide
• CAS: 1085938-58-4
• 化学式: C₂₃H₂₁N₅O₃S
• 分子量: 447.517
• InChiKey: ILVXQPRFMVXZRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-噻吩甲酸 、 N-[2-amino-1-(3-amino-3-oxopropyl)-1H-benzimidazol-5-yl]-N-methylbenzamide 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-[1-(3-amino-3-oxopropyl)-5-[benzoyl(methyl)amino]benzimidazol-2-yl]thiophene-2-carboxamide
  参考文献：
  名称：

  Itk kinase inhibitors: Initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead

  摘要：

  Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.017

文献信息

• Itk kinase inhibitors: Initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead
  作者：Kevin J. Moriarty、Michael Winters、Lei Qiao、Declan Ryan、Renee DesJarlis、Darius Robinson、Brian N. Cook、Mohammed A. Kashem、Paul V. Kaplita、Lisa H. Liu、Thomas M. Farrell、Hnin Hnin Khine、Josephine King、Steven S. Pullen、Gregory P. Roth、Ronald Magolda、Hidenori Takahashi

  DOI：10.1016/j.bmcl.2008.09.017

  日期：2008.10

  Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified. (c) 2008 Elsevier Ltd. All rights reserved.
• Discovery of potent inhibitors of interleukin-2 inducible T-cell kinase (ITK) through structure-based drug design
  作者：Brian N. Cook、Jörg Bentzien、Andre White、Peter A. Nemoto、Ji Wang、Chuk C. Man、Fariba Soleymanzadeh、Hnin Hnin Khine、Mohammed A. Kashem、Stanley Z. Kugler、John P. Wolak、Gregory P. Roth、Stéphane De Lombaert、Steven S. Pullen、Hidenori Takahashi

  DOI：10.1016/j.bmcl.2008.12.028

  日期：2009.2

  Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhibitors through structure-based design where high-resolution crystal structural information was used to optimize interactions within the kinase specificity pocket of the enzyme to improve both potency and selectivity. (C) 2009 Elsevier Ltd. All rights reserved.