1-(3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl)piperidine-4-carboxamide | 1254327-68-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl)piperidine-4-carboxamide
• 英文别名: 1-[3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl]piperidine-4-carboxamide
• CAS: 1254327-68-8
• 化学式: C₁₉H₂₅N₅O₄
• 分子量: 387.439
• InChiKey: CRKNYDXBTAQIBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯硼酸 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 乙二醇二甲醚 、 水 为溶剂， 反应 1.75h， 生成 1-(3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl)piperidine-4-carboxamide
  参考文献：
  名称：

  Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization

  摘要：

  We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.

  DOI：

  10.1021/jm1008727

文献信息

• Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization
  作者：Daniel K. Whelligan、Savade Solanki、Dawn Taylor、Douglas W. Thomson、Kwai-Ming J. Cheung、Kathy Boxall、Corine Mas-Droux、Caterina Barillari、Samantha Burns、Charles G. Grummitt、Ian Collins、Rob L. M. van Montfort、G. Wynne Aherne、Richard Bayliss、Swen Hoelder

  DOI：10.1021/jm1008727

  日期：2010.11.11

  We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.