2-(2,3-difluorophenyl)-5-((5-(4-propoxy-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)methyl)-5H-imidazo[4,5-d]pyridazine | 1186483-83-9

• 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-(2,3-difluorophenyl)-5-((5-(4-propoxy-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)methyl)-5H-imidazo[4,5-d]pyridazine
• 英文别名: 2-(2,3-Difluorophenyl)-5-[[5-[4-propoxy-2-(trifluoromethyl)phenyl]pyrimidin-2-yl]methyl]imidazo[4,5-d]pyridazine
• CAS: 1186483-83-9
• 化学式: C₂₆H₁₉F₅N₆O
• 分子量: 526.468
• InChiKey: AIRDHHYGTQYZTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  78.6
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5-溴-2-氰基嘧啶 在 四(三苯基膦)钯 、 甲酸 、 sodium carbonate 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 38.0h， 生成 2-(2,3-difluorophenyl)-5-((5-(4-propoxy-2-(trifluoromethyl)phenyl)pyrimidin-2-yl)methyl)-5H-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

• ANTI-VIRAL COMPOUNDS, COMPOSITIONS, AND METHODS OF USE
  申请人：Leivers Martin Robert

  公开号：US20090226398A1

  公开（公告）日：2009-09-10

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

  披露了公式(I)的化合物和组合物、药物可接受的盐和溶剂化物，以及它们的制备和使用，用于治疗至少部分由黄病毒科病毒家族中的病毒介导的病毒感染。
• [EN] DERIVATIVES OF IMIDAZO [4, 5-D] PYRIDAZINE AND THEIR USE AS ANTI-VIRAL COMPOUNDS<br/>[FR] DÉRIVÉS D'IMIDAZO[4,5-D]PYRIDAZINE ET LEUR UTILISATION EN TANT QUE COMPOSÉS ANTIVIRAUX
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009111501A1

  公开（公告）日：2009-09-11

  Disclosed are compounds and compositions of Formula (I), pharmaceutically acceptable salts and solvates thereof, and 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.