8-[(dimethylamino)methylidene]-7,8-dihydro-5H-pyrido[3,2-b]azepine-6,9-dione | 1215292-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 8-[(dimethylamino)methylidene]-7,8-dihydro-5H-pyrido[3,2-b]azepine-6,9-dione
• 英文别名: 8-(dimethylaminomethylidene)-5H-pyrido[3,2-b]azepine-6,9-dione
• CAS: 1215292-56-0
• 化学式: C₁₂H₁₃N₃O₂
• 分子量: 231.254
• InChiKey: ZRWHWTHVGFVSNF-UHFFFAOYSA-N

物化性质

• 熔点：
  265 °C (decomp)(Solvent: Ethanol)
• 沸点：
  457.7±45.0 °C(predicted)
• 密度：
  1.304±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.05
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  62.3
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1,3-二甲基-6-氨基脲嘧啶 、 8-[(dimethylamino)methylidene]-7,8-dihydro-5H-pyrido[3,2-b]azepine-6,9-dione 在 溶剂黄146 、 sodium acetate 作用下， 以 水 为溶剂， 反应 7.0h， 以39%的产率得到10,12-dimethyl-7,12-dihydro-5H-pyrido[3,2-b]pyrimido[5',4':5,6]pyrido[2,3-d]azepine-6,9,11(10H)-trione
  参考文献：
  名称：

  Identification of 2-Anilino-9-methoxy-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-ones as Dual PLK1/VEGF-R2 Kinase Inhibitor Chemotypes by Structure-Based Lead Generation

  摘要：

  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.

  DOI：

  10.1021/jm901388c
• 作为产物：
  描述：

  N,N-二甲基甲酰胺 、 5H-吡啶并[3,2-b]氮杂卓-6,9-(7H,8H)-二酮 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.5h， 以42%的产率得到8-[(dimethylamino)methylidene]-7,8-dihydro-5H-pyrido[3,2-b]azepine-6,9-dione
  参考文献：
  名称：

  Identification of 2-Anilino-9-methoxy-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-ones as Dual PLK1/VEGF-R2 Kinase Inhibitor Chemotypes by Structure-Based Lead Generation

  摘要：

  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.

  DOI：

  10.1021/jm901388c