N-(2-(4-(3-cyclopentyl-4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-hydroxybutyl)-2-fluorophenyl)propan-2-yl)methanesulfonamide | 945619-23-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-(4-(3-cyclopentyl-4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-hydroxybutyl)-2-fluorophenyl)propan-2-yl)methanesulfonamide
• CAS: 945619-23-8
• 化学式: C₂₅H₃₆FNO₆S
• 分子量: 497.628
• InChiKey: ACZDKUIDKYXVRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.05
• 重原子数：
  34.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  101.93
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-(2-(4-(3-cyclopentyl-4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-hydroxybutyl)-2-fluorophenyl)propan-2-yl)methanesulfonamide 在 dimethyl sulfide borane 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 N-{1-[4-(2-{2-cyclopentyl-5-[(5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl]-4-hydroxy-6-oxo-3,6-dihydro-2H-pyran-2-yl}ethyl)-2-fluorophenyl]-1-methylethyl}methanesulfonamide
  参考文献：
  名称：

  Allosteric Inhibitors of Hepatitis C Polymerase:  Discovery of Potent and Orally Bioavailable Carbon-Linked Dihydropyrones

  摘要：

  The discovery and optimization of a novel class of carbon-linked dihydropyrones as allosteric HCV NS5B polymerase inhibitors are presented. Replacement of the sulfur linker atom with carbon reduced compound acidity and greatly increased cell permeation. Further structure-activity relationship (SAR) studies led to the identification of compounds, exemplified by 23 and 24, with significantly improved antiviral activities in the cell-based replicon assay and favorable pharmacokinetic profiles.

  DOI：

  10.1021/jm0704447
• 作为产物：
  描述：

  2,2,6-三甲基-4H-1,3-二英-4-酮 在 bis-triphenylphosphine-palladium(II) chloride 、 palladium dihydroxide 、 copper(l) iodide 氢气 、 二异丙胺 、 cesium fluoride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 N-(2-(4-(3-cyclopentyl-4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-hydroxybutyl)-2-fluorophenyl)propan-2-yl)methanesulfonamide
  参考文献：
  名称：

  Allosteric Inhibitors of Hepatitis C Polymerase:  Discovery of Potent and Orally Bioavailable Carbon-Linked Dihydropyrones

  摘要：

  The discovery and optimization of a novel class of carbon-linked dihydropyrones as allosteric HCV NS5B polymerase inhibitors are presented. Replacement of the sulfur linker atom with carbon reduced compound acidity and greatly increased cell permeation. Further structure-activity relationship (SAR) studies led to the identification of compounds, exemplified by 23 and 24, with significantly improved antiviral activities in the cell-based replicon assay and favorable pharmacokinetic profiles.

  DOI：

  10.1021/jm0704447