2-(diethylamino)-N-[3-[5-hydroxy-2-isopentyl-3-oxo-6-(2-thienyl)pyridazin-4-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]ethanesulfonamide | 1042975-88-1

• 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: 2-(diethylamino)-N-[3-[5-hydroxy-2-isopentyl-3-oxo-6-(2-thienyl)pyridazin-4-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]ethanesulfonamide
• 英文别名: 2-(diethylamino)-N-[3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-thiophen-2-ylpyridazin-4-yl]-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-7-yl]ethanesulfonamide
• CAS: 1042975-88-1
• 化学式: C₂₆H₃₄N₆O₆S₃
• 分子量: 622.791
• InChiKey: XUYNPGDPUWXDRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  206
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  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 、 2-(Diethylamino)ethane-1-sulfonamide 在 copper(l) iodide 、 肌氨酸 、 磷酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 2-(diethylamino)-N-[3-[5-hydroxy-2-isopentyl-3-oxo-6-(2-thienyl)pyridazin-4-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]ethanesulfonamide
  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 3: Further optimization of the 2-, 6-, and 7′-substituents and initial pharmacokinetic assessments

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2008.02.072

文献信息

• 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.