(S)-4'-<<4-(2,2,4-trimethyl-1,3-dioxolan-4-yl)thien-2-yl>thio>acetophenone O-(cyanomethyl)oxime | 171482-66-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (S)-4'-<<4-(2,2,4-trimethyl-1,3-dioxolan-4-yl)thien-2-yl>thio>acetophenone O-(cyanomethyl)oxime
• CAS: 171482-66-9
• 化学式: C₂₀H₂₂N₂O₃S₂
• 分子量: 402.538
• InChiKey: WULDPTYAYLVPBD-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.16
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  63.84
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (S)-4'-<<4-(2,2,4-trimethyl-1,3-dioxolan-4-yl)thien-2-yl>thio>acetophenone O-(cyanomethyl)oxime 在 oxone 、 sodium acetate 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 以72%的产率得到[1-{4-[4-((S)-2,2,4-Trimethyl-[1,3]dioxolan-4-yl)-thiophene-2-sulfonyl]-phenyl}-eth-(E)-ylideneaminooxy]-acetonitrile
  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：

  (S)-4'-<<4-(2,2,4-trimethyl-1,3-dioxolan-4-yl)thien-2-yl>thio>acetophenone 在 盐酸羟胺 、 sodium acetate 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 5.5h， 生成 (S)-4'-<<4-(2,2,4-trimethyl-1,3-dioxolan-4-yl)thien-2-yl>thio>acetophenone O-(cyanomethyl)oxime
  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