6-(4-cyanophenyl)[5H]pyrrolo[2,3-b]pyrazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 6-(4-cyanophenyl)[5H]pyrrolo[2,3-b]pyrazine
• 英文别名: 4-{5H-pyrrolo[2,3-b]pyrazin-6-yl}benzonitrile；4-(5H-pyrrolo[2,3-b]pyrazin-6-yl)benzonitrile
• 化学式: C₁₃H₈N₄
• 分子量: 220.233
• InChiKey: LJVIXSSNTIXTNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-甲基吡嗪 、 对苯二腈 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以6%的产率得到6-(4-cyanophenyl)[5H]pyrrolo[2,3-b]pyrazine
  参考文献：
  名称：

  Aloisines, a New Family of CDK/GSK-3 Inhibitors. SAR Study, Crystal Structure in Complex with CDK2, Enzyme Selectivity, and Cellular Effects

  摘要：

  Cyclin-dependent kinases (CDKs) regulate the cell cycle, apoptosis, neuronal functions, transcription, and exocytosis. The observation of CDK deregulations in various pathological situations suggests that CDK inhibitors may have a therapeutic value. In this article, we report on the identification of 6-phenyl[5H]pyrrolo[2,3-b]pyrazines (aloisines) as a novel potent CDK inhibitory scaffold. A selectivity study performed on 26 kinases shows that aloisine A is highly selective for CDK1/cyclin B, CDK2/cyclin A-E, CDK5/p25, and GSK-3alpha/beta; the two latter enzymes have been implicated in Alzheimer's disease. Kinetic studies, as well as the resolution of a CDK2-aloisine cocrystal structure, demonstrate that aloisines act by competitive inhibition of ATP binding to the catalytic subunit of the kinase. As observed with all inhibitors reported so far, aloisine interacts with the ATP-binding pocket through two hydrogen bonds with backbone nitrogen and oxygen atoms of Leu 83. Aloisine inhibits cell proliferation by arresting cells in both G1 and G2.

  DOI：

  10.1021/jm020319p

文献信息

• An improved method for the synthesis of 6-substituted-5H-pyrrolo[2,3-b]pyrazines via palladium-catalyzed heteroannulation using microwave heating
  作者：Corey R. Hopkins、Nicola Collar

  DOI：10.1016/j.tetlet.2004.09.152

  日期：2004.11

  We herein report an improved synthesis of 6-substituted-5H-pyrrolo[2,3-b]pyrazines utilizing microwave heating. The reaction is a palladium-catalyzed heteroannulation process followed by deprotection to yield the desired substrates in good yield.

  我们在本文中报道了利用微波加热的6-取代的-5 H-吡咯并[2，3- b ]吡嗪的改进的合成。该反应是钯催化的异环化工艺，然后进行脱保护，以高收率得到所需的底物。
• Aloisines, a New Family of CDK/GSK-3 Inhibitors. SAR Study, Crystal Structure in Complex with CDK2, Enzyme Selectivity, and Cellular Effects
  作者：Yvette Mettey、Marie Gompel、Virginie Thomas、Matthieu Garnier、Maryse Leost、Irène Ceballos-Picot、Martin Noble、Jane Endicott、Jean-michel Vierfond、Laurent Meijer

  DOI：10.1021/jm020319p

  日期：2003.1.1

  Cyclin-dependent kinases (CDKs) regulate the cell cycle, apoptosis, neuronal functions, transcription, and exocytosis. The observation of CDK deregulations in various pathological situations suggests that CDK inhibitors may have a therapeutic value. In this article, we report on the identification of 6-phenyl[5H]pyrrolo[2,3-b]pyrazines (aloisines) as a novel potent CDK inhibitory scaffold. A selectivity study performed on 26 kinases shows that aloisine A is highly selective for CDK1/cyclin B, CDK2/cyclin A-E, CDK5/p25, and GSK-3alpha/beta; the two latter enzymes have been implicated in Alzheimer's disease. Kinetic studies, as well as the resolution of a CDK2-aloisine cocrystal structure, demonstrate that aloisines act by competitive inhibition of ATP binding to the catalytic subunit of the kinase. As observed with all inhibitors reported so far, aloisine interacts with the ATP-binding pocket through two hydrogen bonds with backbone nitrogen and oxygen atoms of Leu 83. Aloisine inhibits cell proliferation by arresting cells in both G1 and G2.