4-[7-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[e][1,2,4]thiadiazin-3-yl]-5-hydroxy-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazin-3-one | 1038402-72-0

• 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: 4-[7-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[e][1,2,4]thiadiazin-3-yl]-5-hydroxy-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazin-3-one
• 英文别名: 4-[7-(1,1-dioxo-1,2-thiazolidin-2-yl)-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-3-yl]-5-hydroxy-2-isopentyl-6-(2-thienyl)pyridazin-3-one；4-[7-(1,1-dioxo-1,2-thiazolidin-2-yl)-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-3-yl]-5-hydroxy-2-(3-methylbutyl)-6-thiophen-2-ylpyridazin-3-one
• CAS: 1038402-72-0
• 化学式: C₂₃H₂₅N₅O₆S₃
• 分子量: 563.679
• InChiKey: QIJJBUOXNZDPGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  194
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  异噻唑烷 1,1-二氧化物 、 5-hydroxy-4-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[e][1,2,4]thiadiazin-3-yl)-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazin-3-one 在 copper(l) iodide potassium phosphate 、 肌氨酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 以28%的产率得到4-[7-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[e][1,2,4]thiadiazin-3-yl]-5-hydroxy-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazin-3-one
  参考文献：
  名称：

  WO2008/82725

  摘要：

  公开号：

文献信息

• Pyridazinone compounds
  申请人：Zhou Yuefen

  公开号：US20080275032A1

  公开（公告）日：2008-11-06

  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咪唑酮化合物以及包含这些化合物的药物组合物，这些化合物在治疗丙型肝炎病毒感染方面具有用处。
• WO2008/82725
  申请人：——

  公开号：——

  公开（公告）日：——
• 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 3: Further optimization of the 2-, 6-, and 7′-substituents and initial pharmacokinetic assessments
  作者：Lian-Sheng Li、Yuefen Zhou、Douglas E. Murphy、Nebojsa Stankovic、Jingjing Zhao、Peter S. Dragovich、Thomas Bertolini、Zhongxiang Sun、Benjamin Ayida、Chinh V. Tran、Frank Ruebsam、Stephen E. Webber、Amit M. Shah、Mei Tsan、Richard E. Showalter、Rupal Patel、Laurie A. LeBrun、Darian M. Bartkowski、Thomas G. Nolan、Daniel A. Norris、Ruhi Kamran、Jennifer Brooks、Maria V. Sergeeva、Leo Kirkovsky、Qiang Zhao、Charles R. Kissinger

  DOI：10.1016/j.bmcl.2008.02.072

  日期：2008.6

  5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. Lead optimization led to the discovery of compound 3a, which displayed potent inhibitory activities in biochemical and replicon assays [IC50 (1b) < 10 nM; IC50 (1a) = 22 nM; EC50 (1b) = 5 nM], good stability toward human liver microsomes (HLM t(1/2) > 60 min), and high ratios of liver to plasma concentrations 12 h after a single oral administration to rats. (c) 2008 Published by Elsevier Ltd.