N-[(2E)-5-[benzene(methyl)amido]-1-(2-carbamoylethyl)-2,3-dihydro-1H-1,3-benzodiazol-2-ylidene]-5-acetylthiophene-2-carboxamide | 1092486-13-9

• 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-[(2E)-5-[benzene(methyl)amido]-1-(2-carbamoylethyl)-2,3-dihydro-1H-1,3-benzodiazol-2-ylidene]-5-acetylthiophene-2-carboxamide
• 英文别名: 5-acetyl-N-[1-(3-amino-3-oxopropyl)-5-[benzoyl(methyl)amino]benzimidazol-2-yl]thiophene-2-carboxamide
• CAS: 1092486-13-9
• 化学式: C₂₅H₂₃N₅O₄S
• 分子量: 489.555
• InChiKey: UBOPXWHTIVENRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(2E)-5-[benzene(methyl)amido]-1-(2-carbamoylethyl)-2,3-dihydro-1H-1,3-benzodiazol-2-ylidene]-5-acetylthiophene-2-carboxamide 、 (氰基甲基)三苯基溴化膦 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 生成 N-[1-(3-amino-3-oxopropyl)-5-[benzoyl(methyl)amino]benzimidazol-2-yl]-5-(1-cyanoprop-1-en-2-yl)thiophene-2-carboxamide
  参考文献：
  名称：

  2-Aminobenzimidazoles as potent ITK antagonists: trans-stilbene-like moieties targeting the kinase specificity pocket

  摘要：

  Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel ITK antagonists. Significant improvement on binding affinity and cellular activity were obtained through the trans-stilbene-like antagonists. Several compounds showed inhibitory activity in an IL-2 functional assay. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.098
• 作为产物：
  描述：

  5-乙酰基噻吩-2-甲酸 、 N-[2-amino-1-(3-amino-3-oxopropyl)-1H-benzimidazol-5-yl]-N-methylbenzamide 在 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， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-[(2E)-5-[benzene(methyl)amido]-1-(2-carbamoylethyl)-2,3-dihydro-1H-1,3-benzodiazol-2-ylidene]-5-acetylthiophene-2-carboxamide
  参考文献：
  名称：

  Discovery of potent inhibitors of interleukin-2 inducible T-cell kinase (ITK) through structure-based drug design

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2008.12.028

文献信息

• 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.
• 2-Aminobenzimidazoles as potent ITK antagonists: trans-stilbene-like moieties targeting the kinase specificity pocket
  作者：Ho Yin Lo、Jörg Bentzien、Roman W. Fleck、Steven S. Pullen、Hnin Hnin Khine、Joseph R. Woska、Stanley Z. Kugler、Mohammed A. Kashem、Hidenori Takahashi

  DOI：10.1016/j.bmcl.2008.09.098

  日期：2008.12

  Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel ITK antagonists. Significant improvement on binding affinity and cellular activity were obtained through the trans-stilbene-like antagonists. Several compounds showed inhibitory activity in an IL-2 functional assay. (C) 2008 Elsevier Ltd. All rights reserved.