ethyl 7-[(dimethylamino)methylidene]-6-oxo-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-2-carboxylate | 871112-22-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 7-[(dimethylamino)methylidene]-6-oxo-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-2-carboxylate
• 英文别名: ethyl 7-[(dimethylamino)methylene]-6-oxo-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-2-carboxylate；Ethyl 7-(dimethylaminomethylidene)-6-oxo-5,8,9,10-tetrahydrocyclohepta[b]indole-2-carboxylate
• CAS: 871112-22-0
• 化学式: C₁₉H₂₂N₂O₃
• 分子量: 326.395
• InChiKey: VOPCLGPVBUDCQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  62.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 7-[(dimethylamino)methylidene]-6-oxo-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-2-carboxylate 在 水 、 一水合肼 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 91.0h， 生成 4,5,6,11-tetrahydro-2H-pyrazolo[4',3':6,7]cyclohepta[1,2-b]indole-8-carboxylic acid
  参考文献：
  名称：

  A Back-to-Front Fragment-Based Drug Design Search Strategy Targeting the DFG-Out Pocket of Protein Tyrosine Kinases

  摘要：

  We present a straightforward process for the discovery of novel back pocket-binding fragment molecules against protein tyrosine kinases. The approach begins by screening against the nonphosphorylated target kinase with subsequent counterscreening of hits against the phosphorylated enzyme. Back pocket-binding fragments are inactive against the phosphorylated kinase. Fragment molecules are of insufficient size to span both regions of the ATP binding pocket; thus, the outcome is binary (back pocket-binding or hinge-binding). Next, fragments with the appropriate binding profile are assayed in combination with a known hinge-binding fragment and subsequently with a known back pocket-binding fragment. Confirmation of back pocket-binding by Yonetani-Theorell plot analysis progresses candidate fragments to crystallization trials. The method is exemplified by a fragment screening campaign against vascular endothelial growth factor receptor 2, and a novel back pocket-binding fragment is presented.

  DOI：

  10.1021/ml3000403
• 作为产物：
  描述：

  ethyl 4-[2-(2-oxocycloheptylidene)hydrazino]benzoate 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 ethyl 7-[(dimethylamino)methylidene]-6-oxo-5,6,7,8,9,10-hexahydrocyclohepta[b]indole-2-carboxylate
  参考文献：
  名称：

  A Back-to-Front Fragment-Based Drug Design Search Strategy Targeting the DFG-Out Pocket of Protein Tyrosine Kinases

  摘要：

  We present a straightforward process for the discovery of novel back pocket-binding fragment molecules against protein tyrosine kinases. The approach begins by screening against the nonphosphorylated target kinase with subsequent counterscreening of hits against the phosphorylated enzyme. Back pocket-binding fragments are inactive against the phosphorylated kinase. Fragment molecules are of insufficient size to span both regions of the ATP binding pocket; thus, the outcome is binary (back pocket-binding or hinge-binding). Next, fragments with the appropriate binding profile are assayed in combination with a known hinge-binding fragment and subsequently with a known back pocket-binding fragment. Confirmation of back pocket-binding by Yonetani-Theorell plot analysis progresses candidate fragments to crystallization trials. The method is exemplified by a fragment screening campaign against vascular endothelial growth factor receptor 2, and a novel back pocket-binding fragment is presented.

  DOI：

  10.1021/ml3000403