6,7-二氢-9-羟基-6-氧代-5H-吡啶并[3,2-b]氮杂卓-8-羧酸乙酯 | 676596-62-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 中文名称: 6,7-二氢-9-羟基-6-氧代-5H-吡啶并[3,2-b]氮杂卓-8-羧酸乙酯
• 英文名称: 6,7-Dihydro-9-hydroxy-6-oxo-5H-pyrido[3,2-b]azepine-8-carboxylic Acid Ethyl Ester
• 英文别名: ethyl 9-hydroxy-6-oxo-5,7-dihydropyrido[3,2-b]azepine-8-carboxylate
• CAS: 676596-62-6
• 化学式: C₁₂H₁₂N₂O₄
• 分子量: 248.238
• InChiKey: RXKNXEINJYMUOD-UHFFFAOYSA-N

物化性质

• 熔点：
  216-219°C (dec.)
• 溶解度：
  可溶于氯仿（少量）、二氯甲烷（少量）、乙酸乙酯（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,7-二氢-9-羟基-6-氧代-5H-吡啶并[3,2-b]氮杂卓-8-羧酸乙酯 在 盐酸 、 水 、 sodium acetate 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 生成 7,8-二氢-9-[2-(4-溴苯基)腙]-5H-吡啶并[3,2-b]氮杂卓-6,9-二酮
  参考文献：
  名称：

  1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3β

  摘要：

  Kenpaullone derivatives with a modified parent ring system were synthesized in order to develop kinase inhibitors with enhanced selectivity. Among the novel structures, 1-azakenpaullone was found to act as a selective GSK-3beta versus CDK1 inhibitor. The charge distribution within the 1-azakenpaullone molecule is discussed as a possible explanation for the enhanced GSK-3beta selectivity of 1-azakenpaullone compared to other paullone derivatives. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.062
• 作为产物：
  描述：

  3-氨基吡啶-2-甲酸乙酯 在 吡啶 、 potassium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 6,7-二氢-9-羟基-6-氧代-5H-吡啶并[3,2-b]氮杂卓-8-羧酸乙酯
  参考文献：
  名称：

  1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3β

  摘要：

  Kenpaullone derivatives with a modified parent ring system were synthesized in order to develop kinase inhibitors with enhanced selectivity. Among the novel structures, 1-azakenpaullone was found to act as a selective GSK-3beta versus CDK1 inhibitor. The charge distribution within the 1-azakenpaullone molecule is discussed as a possible explanation for the enhanced GSK-3beta selectivity of 1-azakenpaullone compared to other paullone derivatives. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.062

文献信息

• 9-Cyano-1-azapaullone (Cazpaullone), a Glycogen Synthase Kinase-3 (GSK-3) Inhibitor Activating Pancreatic β Cell Protection and Replication
  作者：Hendrik Stukenbrock、Rainer Mussmann、Marcus Geese、Yoan Ferandin、Olivier Lozach、Thomas Lemcke、Simone Kegel、Alexander Lomow、Ulrike Burk、Cord Dohrmann、Laurent Meijer、Matthias Austen、Conrad Kunick

  DOI：10.1021/jm701582f

  日期：2008.4.1

  Recently, the serine/threonine kinase glycogen synthase kinase-3 (GSK-3) emerged as a regulator of pancreatic beta cell growth and survival. On the basis of the previous observation that GSK-3 inhibitors like 1-azakenpaullone promote beta cell protection and replication, paullone derivatives were synthesized including 1-aza-, 2-aza-, and 12-oxapaullone scaffolds. In enzymatic assays distinct 1-azapaullones were found to exhibit selective GSK-3 inhibitory activity. Within the series of 1-azapaullones, three derivatives stimulated INS-1E beta cell replication and protected INS-1E cells against glucolipotoxicity induced cell death. Cazpaullone (9-cyano-1-azapaullone), the most active compound in the protection assays, also stimulated the replication of primary beta cells in isolated rat islets. Furthermore, cazpaullone showed a pronounced transient stimulation of the mRNA expression of the beta cell transcription factor Pax4, an important regulator of beta cell development and growth. These features distinguish cazpaullone as a unique starting point for the development of beta cell regenerative agents which might be useful in the treatment of diabetes.
• 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3β
  作者：Conrad Kunick、Kathrin Lauenroth、Maryse Leost、Laurent Meijer、Thomas Lemcke

  DOI：10.1016/j.bmcl.2003.10.062

  日期：2004.1

  Kenpaullone derivatives with a modified parent ring system were synthesized in order to develop kinase inhibitors with enhanced selectivity. Among the novel structures, 1-azakenpaullone was found to act as a selective GSK-3beta versus CDK1 inhibitor. The charge distribution within the 1-azakenpaullone molecule is discussed as a possible explanation for the enhanced GSK-3beta selectivity of 1-azakenpaullone compared to other paullone derivatives. (C) 2003 Elsevier Ltd. All rights reserved.