2-(5-Methylsulfanyl-thiophen-3-yl)-1-(tetrahydro-pyran-2-yloxy)-propan-2-ol | 159615-90-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(5-Methylsulfanyl-thiophen-3-yl)-1-(tetrahydro-pyran-2-yloxy)-propan-2-ol
• 英文别名: 2-(5-Methylsulfanylthiophen-3-yl)-1-(oxan-2-yloxy)propan-2-ol
• CAS: 159615-90-4
• 化学式: C₁₃H₂₀O₃S₂
• 分子量: 288.432
• InChiKey: OWQMRNLRLWMTNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  92.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(5-Methylsulfanyl-thiophen-3-yl)-1-(tetrahydro-pyran-2-yloxy)-propan-2-ol 在 盐酸 、 potassium carbonate 、 对甲苯磺酸 、 sodium thiomethoxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 4.25h， 生成 4'-<<4-(2,2,4-trimethyl-1,3-dioxolan-4-yl)thien-2-yl>thio>acetophenone
  参考文献：
  名称：

  Chiral Dioxolane Inhibitors of Leukotriene Biosynthesis: Structure-Activity Relationships and Syntheses Using Asymmetric Dihydroxylation

  摘要：

  1,3-Dioxolanes have been described as chiral inhibitors of 5-lipoxygenase (5LO). In the present work, this series has been developed further to provide agents which showed comparable or superior potency in vivo to ZD2138, a methoxytetrahydropyran inhibitor of 5LO, which is currently undergoing clinical evaluation. An asymmetric synthesis was developed to these dioxolanes based on asymmetric dihydroxylation. (S)-N-Methyl-4'-[[4-(2,2,4-trimethyl-1,3 dioxolan-4-yl)thien-2-yl]thio]acetanilid ((S)-10d) inhibited leukotriene B-4 (LTB(4)) synthesis in A23187-stimulated human whole blood in vitro with IC50 0.039 mu M, 25-fold more potent than (R)-10d. In vivo, (S)-10d inhibited LTB(4) synthesis by 70% in zymosan-inflamed air pouch exudate in rat 10 h after an oral dose of 1.5 mg/kg. Structure-activity relationship considerations suggested that the dioxolane and methoxytetrahydropyran series are related, a conclusion which can be supported by molecular modeling.

  DOI：

  10.1021/jm00020a008
• 作为产物：
  描述：

  1-hydroxypropan-2-one tetrahydropyran ether 、 4-bromo-2-(methylthio)thiophene 在 正丁基锂 作用下， 生成 2-(5-Methylsulfanyl-thiophen-3-yl)-1-(tetrahydro-pyran-2-yloxy)-propan-2-ol
  参考文献：
  名称：

  Chiral Dioxolane Inhibitors of Leukotriene Biosynthesis: Structure-Activity Relationships and Syntheses Using Asymmetric Dihydroxylation

  摘要：

  1,3-Dioxolanes have been described as chiral inhibitors of 5-lipoxygenase (5LO). In the present work, this series has been developed further to provide agents which showed comparable or superior potency in vivo to ZD2138, a methoxytetrahydropyran inhibitor of 5LO, which is currently undergoing clinical evaluation. An asymmetric synthesis was developed to these dioxolanes based on asymmetric dihydroxylation. (S)-N-Methyl-4'-[[4-(2,2,4-trimethyl-1,3 dioxolan-4-yl)thien-2-yl]thio]acetanilid ((S)-10d) inhibited leukotriene B-4 (LTB(4)) synthesis in A23187-stimulated human whole blood in vitro with IC50 0.039 mu M, 25-fold more potent than (R)-10d. In vivo, (S)-10d inhibited LTB(4) synthesis by 70% in zymosan-inflamed air pouch exudate in rat 10 h after an oral dose of 1.5 mg/kg. Structure-activity relationship considerations suggested that the dioxolane and methoxytetrahydropyran series are related, a conclusion which can be supported by molecular modeling.

  DOI：

  10.1021/jm00020a008

文献信息

• Chiral Dioxolane Inhibitors of Leukotriene Biosynthesis: Structure-Activity Relationships and Syntheses Using Asymmetric Dihydroxylation
  作者：Graham C. Crawley、Malcolm T. Briggs

  DOI：10.1021/jm00020a008

  日期：1995.9

  1,3-Dioxolanes have been described as chiral inhibitors of 5-lipoxygenase (5LO). In the present work, this series has been developed further to provide agents which showed comparable or superior potency in vivo to ZD2138, a methoxytetrahydropyran inhibitor of 5LO, which is currently undergoing clinical evaluation. An asymmetric synthesis was developed to these dioxolanes based on asymmetric dihydroxylation. (S)-N-Methyl-4'-[[4-(2,2,4-trimethyl-1,3 dioxolan-4-yl)thien-2-yl]thio]acetanilid ((S)-10d) inhibited leukotriene B-4 (LTB(4)) synthesis in A23187-stimulated human whole blood in vitro with IC50 0.039 mu M, 25-fold more potent than (R)-10d. In vivo, (S)-10d inhibited LTB(4) synthesis by 70% in zymosan-inflamed air pouch exudate in rat 10 h after an oral dose of 1.5 mg/kg. Structure-activity relationship considerations suggested that the dioxolane and methoxytetrahydropyran series are related, a conclusion which can be supported by molecular modeling.