5-((2-(2,3-difluorophenyl)-5H-imidazo[4,5-d]pyridazin-5-yl)methyl)-3-(2-methoxypyrimidin-5-yl)isoxazole | 1174506-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-((2-(2,3-difluorophenyl)-5H-imidazo[4,5-d]pyridazin-5-yl)methyl)-3-(2-methoxypyrimidin-5-yl)isoxazole
• 英文别名: 2-(2,3-Difluoro-phenyl)-5-[3-(2-methoxy-pyrimidin-5-yl)-isoxazol-5-ylmethyl]-5H-imidazo[4,5-d]pyridazine；5-[[2-(2,3-difluorophenyl)imidazo[4,5-d]pyridazin-5-yl]methyl]-3-(2-methoxypyrimidin-5-yl)-1,2-oxazole
• CAS: 1174506-55-8
• 化学式: C₂₀H₁₃F₂N₇O₂
• 分子量: 421.366
• InChiKey: WPNULQGNEPPYCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,3-二氟苯甲醛 在 N-氯代丁二酰亚胺 、 硫酸 、 烟酰胺 、 二异丁基氢化铝 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 5-((2-(2,3-difluorophenyl)-5H-imidazo[4,5-d]pyridazin-5-yl)methyl)-3-(2-methoxypyrimidin-5-yl)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

文献信息

• Anti-Viral Compounds, Compositions, And Methods Of Use
  申请人：Leivers Martin Robert

  公开号：US20110044943A1

  公开（公告）日：2011-02-24

  Disclosed are compounds of Formula (I), pharmaceutically acceptable salts and solvates thereof, compositions thereof, and methods for their preparation and uses for treating viral infections mediated at least in part by a virus in the Flaviviridae family of viruses.

  本发明涉及式（I）的化合物、药学上可接受的盐和溶剂化物、其组合物以及其制备方法和用于治疗由Flaviviridae病毒家族中的病毒至少部分介导的病毒感染的用途。
• ANTI-VIRAL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE
  申请人：Leivers Martin Robert

  公开号：US20090197880A1

  公开（公告）日：2009-08-06

  Disclosed are compounds of Formula (I), pharmaceutically acceptable salts and solvates thereof, compositions thereof, and methods for their preparation and uses for treating viral infections mediated at least in part by a virus in the Flaviviridae family of viruses.

  本发明涉及公式（I）的化合物，其药学上可接受的盐和溶剂化合物，以及其组合物的制备方法和用于治疗由黄病毒科病毒介导的至少部分病毒感染的用途。
• [EN] ANTI-VIRAL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE<br/>[FR] COMPOSÉS ANTIVIRAUX, COMPOSITIONS ET MÉTHODES D'APPLICATION
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010081145A1

  公开（公告）日：2010-07-15

  Disclosed are compounds of Formula (I), pharmaceutically acceptable salts and solvates thereof, compositions thereof, and methods for their preparation and uses for treating viral infections mediated at least in part by a virus in the Flaviviridae family of viruses.
• 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.