5H-吡啶并[3,2-b]氮杂卓-6,9-(7H,8H)-二酮 | 676596-63-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 5H-吡啶并[3,2-b]氮杂卓-6,9-(7H,8H)-二酮
• 英文名称: 5H-pyrido[3,2-b]azepine-6,9(7H,8H)-dione
• 英文别名: 7,8-Dihydro-5H-pyrido[3,2-B]azepine-6,9-dione
• CAS: 676596-63-7
• 化学式: C₉H₈N₂O₂
• mdl: MFCD09817624
• 分子量: 176.175
• InChiKey: UQNHEOOEYBDZCM-UHFFFAOYSA-N

物化性质

• 熔点：
  >161°C (dec.)
• 沸点：
  433.8±40.0 °C(Predicted)
• 密度：
  1.292±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  59.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5H-吡啶并[3,2-b]氮杂卓-6,9-(7H,8H)-二酮 在 盐酸 、 sodium acetate 作用下， 以 二苯醚 、 溶剂黄146 为溶剂， 生成 1-Azakenpaullone
  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 、 水 、 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 5H-吡啶并[3,2-b]氮杂卓-6,9-(7H,8H)-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

文献信息

• Use of Azapaullones For Preventing and Treating Pancreatic Autoimmune Disorders
  申请人：Mussmann Rainer

  公开号：US20080287423A1

  公开（公告）日：2008-11-20

  This invention relates to the use of azapaullones, particularly in combination with immunomodulating agents, in the prevention, and/or treatment of pancreatic autoimmune disorders, e.g. type I diabetes or LADA and neurodegenerative disorders.

  本发明涉及使用阿扎泊隆，特别是与免疫调节剂结合使用，在预防和/或治疗胰腺自身免疫疾病，例如1型糖尿病或LADA和神经退行性疾病方面的应用。
• Use of azapaullones for preventing and treating pancreatic autoimmune disorders
  申请人：Develogen Atkiengesellschaft

  公开号：US07968535B2

  公开（公告）日：2011-06-28

  This invention relates to the use of azapaullones, particularly in combination with immunomodulating agents, in the prevention, and/or treatment of pancreatic autoimmune disorders, e.g. type I diabetes or LADA and neurodegenerative disorders.

  本发明涉及使用阿扎泊隆，特别是与免疫调节剂联合使用，预防和/或治疗胰腺自身免疫疾病，例如I型糖尿病或LADA和神经退行性疾病。
• 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.
• WO2006/117221
  申请人：——

  公开号：——

  公开（公告）日：——
• Identification of 2-Anilino-9-methoxy-5,7-dihydro-6<i>H</i>-pyrimido[5,4-<i>d</i>][1]benzazepin-6-ones as Dual PLK1/VEGF-R2 Kinase Inhibitor Chemotypes by Structure-Based Lead Generation
  作者：Anne-Marie Egert-Schmidt、Jan Dreher、Ute Dunkel、Simone Kohfeld、Lutz Preu、Holger Weber、Jan E. Ehlert、Bettina Mutschler、Frank Totzke、Christoph Schächtele、Michael H. G. Kubbutat、Knut Baumann、Conrad Kunick

  DOI：10.1021/jm901388c

  日期：2010.3.25

  To develop multikinase inhibitors with dual PLK1/VEGF-R2 inhibitory activity, the d-annulated 1-benzazepin-2-one scaffold present in the paullone family of kinase inhibitors was investigated as a general structure template suitable for anchoring annulated heterocycles at the hinge region of the ATP binding site. For this purpose, the indole substructure of the paullones was replaced by other nitrogen containing heteroaromatics. The designed scaffolds were synthesized and tested on the indicated kinases. The 2-anilino-5.7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-ones were found to be VEGF-R2 inhibitors with selectivity against the insulin receptor kinase. The attachment of a methoxy group to the 9-position of the scaffold led to additional PLK1 inhibitory activity, which was explained by an alternative binding mode of the 9-methoxy derivatives. Selected members of the compound class inhibited the VEGF-R2 autophosphorylation in human umbilical vein endothelial cells, the sprouting of human umbilical vein endothelial cell speroids, and the proliferation of diverse cancer cell lines.