2-bromo-1H-imidazo[4,5-d]pyridazine | 1494717-93-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-bromo-1H-imidazo[4,5-d]pyridazine
• 英文别名: 2-bromo-5H-imidazo[4,5-d]pyridazine
• CAS: 1494717-93-9
• 化学式: C₅H₃BrN₄
• 分子量: 199.01
• InChiKey: WGIFRXNLWZKXMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromo-1H-imidazo[4,5-d]pyridazine 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 1.33h， 生成 3-(2,4-bis(trifluoromethyl)phenyl)-5-((2-(2,6-difluorophenyl)-5H-imidazo[4,5-d]pyridazin-5-yl)methyl)isoxazole
  参考文献：
  名称：

  Imidazopyridazine Hepatitis C Virus Polymerase Inhibitors. Structure–Activity Relationship Studies and the Discovery of a Novel, Traceless Prodrug Mechanism

  摘要：

  By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodnig mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.

  DOI：

  10.1021/jm401337x
• 作为产物：
  描述：

  2-溴-4,5-二氰基咪唑 在 二异丁基氢化铝 、 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 1.42h， 以17%的产率得到2-bromo-1H-imidazo[4,5-d]pyridazine
  参考文献：
  名称：

  Imidazopyridazine Hepatitis C Virus Polymerase Inhibitors. Structure–Activity Relationship Studies and the Discovery of a Novel, Traceless Prodrug Mechanism

  摘要：

  By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodnig mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.

  DOI：

  10.1021/jm401337x

文献信息

• KR2015/12974
  申请人：——

  公开号：——

  公开（公告）日：——
• Imidazopyridazine Hepatitis C Virus Polymerase Inhibitors. Structure–Activity Relationship Studies and the Discovery of a Novel, Traceless Prodrug Mechanism
  作者：Martin Leivers、John F. Miller、Stephanie A. Chan、Ryan Lauchli、Sebastian Liehr、Wenyan Mo、Tony Ton、Elizabeth M. Turner、Michael Youngman、J. Greg Falls、Susan Long、Amanda Mathis、Jill Walker

  DOI：10.1021/jm401337x

  日期：2014.3.13

  By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored in order to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodnig mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.