N-{3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-pyrrolidin-1-yl-2,3-dihydropyridazin-4-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide | 1044277-17-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: N-{3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-pyrrolidin-1-yl-2,3-dihydropyridazin-4-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide
• 英文别名: N-[3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-pyrrolidin-1-ylpyridazin-4-yl]-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-7-yl]methanesulfonamide
• CAS: 1044277-17-9
• 化学式: C₂₁H₂₈N₆O₆S₂
• 分子量: 524.622
• InChiKey: QUWPELVBLLLYGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  178
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 吡啶 为溶剂， 生成 N-{3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-pyrrolidin-1-yl-2,3-dihydropyridazin-4-yl]-1,1-dioxido-2H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide
  参考文献：
  名称：

  Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 5: Exploration of pyridazinones containing 6-amino-substituents

  摘要：

  The synthesis of 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones bearing 6-amino substituents as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC(50)<0.10 microM). In vitro DMPK data (microsome t(1/2), Caco-2 P(app)) for many of the compounds are also disclosed, and a crystal structure of a representative inhibitor complexed with the NS5B protein is discussed.

  DOI：

  10.1016/j.bmcl.2008.08.094

文献信息

• PYRIDAZINONE COMPOUNDS
  申请人：Dragovich Peter

  公开号：US20080188466A1

  公开（公告）日：2008-08-07

  The invention is directed to pyridazinone compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.

  这项发明涉及吡啶并酮化合物和含有这些化合物的药物组合物，用于治疗丙型肝炎病毒感染。
• Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 5: Exploration of pyridazinones containing 6-amino-substituents
  作者：Peter S. Dragovich、Julie K. Blazel、David A. Ellis、Qing Han、Ruhi Kamran、Charles R. Kissinger、Laurie A. LeBrun、Lian-Sheng Li、Douglas E. Murphy、Michael Noble、Rupal A. Patel、Frank Ruebsam、Maria V. Sergeeva、Amit M. Shah、Richard E. Showalter、Chinh V. Tran、Mei Tsan、Stephen E. Webber、Leo Kirkovsky、Yuefen Zhou

  DOI：10.1016/j.bmcl.2008.08.094

  日期：2008.10

  The synthesis of 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones bearing 6-amino substituents as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC(50)<0.10 microM). In vitro DMPK data (microsome t(1/2), Caco-2 P(app)) for many of the compounds are also disclosed, and a crystal structure of a representative inhibitor complexed with the NS5B protein is discussed.