ethyl 2-(2,2-dimethylpropyl)-5-hydroxy-3-oxo-6-thiophen-2-yl-2,3-dihydropyridazine-4-carboxylate | 1003322-26-6

• 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: ethyl 2-(2,2-dimethylpropyl)-5-hydroxy-3-oxo-6-thiophen-2-yl-2,3-dihydropyridazine-4-carboxylate
• 英文别名: Ethyl 2-(2,2-dimethylpropyl)-5-hydroxy-3-oxo-6-thiophen-2-ylpyridazine-4-carboxylate；ethyl 2-(2,2-dimethylpropyl)-5-hydroxy-3-oxo-6-thiophen-2-ylpyridazine-4-carboxylate
• CAS: 1003322-26-6
• 化学式: C₁₆H₂₀N₂O₄S
• 分子量: 336.412
• InChiKey: VMMCCPQCDHXGAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-amino-5-(methanesulfonylamino)benzenesulfonamide 、 ethyl 2-(2,2-dimethylpropyl)-5-hydroxy-3-oxo-6-thiophen-2-yl-2,3-dihydropyridazine-4-carboxylate 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 反应 19.0h， 生成 N-{3-[2-(2,2-dimethyl-propyl)-5-hydroxy-3-oxo-6-thiophen-2-yl-2,3-dihydro-pyridazin-4-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[e][1,2,4]thiadiazin-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 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
• 作为产物：
  描述：

  在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 ethyl 2-(2,2-dimethylpropyl)-5-hydroxy-3-oxo-6-thiophen-2-yl-2,3-dihydropyridazine-4-carboxylate
  参考文献：
  名称：

  Synthesis of New Pyridazinone Derivatives: 2,6-Disubstituted 5-Hydroxy-3(2H)-pyridazinone-4-carboxylic Acid Ethyl Esters

  摘要：

  合成了2,6-二取代的5-羟基-3(2H)-吡嗪酮-4-羧酸乙基酯，过程采用了一种高效的三步法，包括肼酮的形成、与乙基美克氯的酰化和随后进行的迪克曼环化。

  DOI：

  10.1055/s-2007-990823

文献信息

• Efficient synthesis of 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters
  作者：Douglas E. Murphy、Peter S. Dragovich、Benjamin K. Ayida、Thomas M. Bertolini、Lian-Sheng Li、Frank Ruebsam、Nebojsa S. Stankovic、Zhongxiang Sun、Jingjing Zhao、Yuefen Zhou

  DOI：10.1016/j.tetlet.2007.11.187

  日期：2008.1

  boxylic acid ethyl esters (6-substituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters). These compounds are shown to undergo selective alkylation at the 2-position in moderate to good yields (19–77%) to afford 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters (2,6-disubstituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters).

  描述了用于制备6-取代的5-羟基-3-氧代-2,3-二氢哒嗪-4-羧酸乙酯（6-取代的-5-羟基-3（2 H）-哒嗪酮-4-羧酸乙酯）。这些化合物显示在2位发生选择性烷基化，产率中等至良好（19-77％），可提供2,6-二取代的-5-羟基-3-羟基-3-氧代-2,3-二氢哒嗪-4-羧酸乙酯（2，6-二取代-5-羟基-3（2 H）-哒嗪酮-4-羧酸乙酯）。
• 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.
• Synthesis of New Pyridazinone Derivatives: 2,6-Disubstituted 5-Hydroxy-3(2<i>H</i>)-pyridazinone-4-carboxylic Acid Ethyl Esters
  作者：Yuefen Zhou、Lian-Sheng Li、Jingjing Zhao、Peter Dragovich、Nebojsa Stankovic、Thomas Bertolini、Douglas Murphy、Zhongxiang Sun、Chinh Tran、Benjamin Ayida、Frank Ruebsam、Stephen Webber

  DOI：10.1055/s-2007-990823

  日期：2007.11

  2,6-Disubstituted 5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters were synthesized from α-keto esters via an efficient three-step sequence including hydrazone formation, acylation with ethyl malonyl chloride, and subsequent Dieckmann cyclization.

  合成了2,6-二取代的5-羟基-3(2H)-吡嗪酮-4-羧酸乙基酯，过程采用了一种高效的三步法，包括肼酮的形成、与乙基美克氯的酰化和随后进行的迪克曼环化。