3-iodo-4-[2-(6-oxo-5,6,7,8-tetrahydro-9H-pyrido[3,2-b]azepine-9-ylidene)hydrazino]benzonitrile | 1019995-22-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-iodo-4-[2-(6-oxo-5,6,7,8-tetrahydro-9H-pyrido[3,2-b]azepine-9-ylidene)hydrazino]benzonitrile
• CAS: 1019995-22-2
• 化学式: C₁₆H₁₂IN₅O
• 分子量: 417.209
• InChiKey: JSGGGPILTYXYGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.11
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  90.17
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-iodo-4-[2-(6-oxo-5,6,7,8-tetrahydro-9H-pyrido[3,2-b]azepine-9-ylidene)hydrazino]benzonitrile 以 二苯醚 为溶剂， 反应 2.0h， 生成 16-Iodo-9-oxo-3,8,18-triazatetracyclo[9.7.0.02,7.012,17]octadeca-1(11),2(7),3,5,12(17),13,15-heptaene-14-carbonitrile
  参考文献：
  名称：

  9-Cyano-1-azapaullone (Cazpaullone), a Glycogen Synthase Kinase-3 (GSK-3) Inhibitor Activating Pancreatic β Cell Protection and Replication

  摘要：

  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.

  DOI：

  10.1021/jm701582f
• 作为产物：
  描述：

  4-hydrazino-3-iodobenzonitrile hydrochloride 、 5H-吡啶并[3,2-b]氮杂卓-6,9-(7H,8H)-二酮 在 sodium acetate 、 溶剂黄146 作用下， 以26%的产率得到3-iodo-4-[2-(6-oxo-5,6,7,8-tetrahydro-9H-pyrido[3,2-b]azepine-9-ylidene)hydrazino]benzonitrile
  参考文献：
  名称：

  9-Cyano-1-azapaullone (Cazpaullone), a Glycogen Synthase Kinase-3 (GSK-3) Inhibitor Activating Pancreatic β Cell Protection and Replication

  摘要：

  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.

  DOI：

  10.1021/jm701582f