2-(4-fluorophenyl)-N-(4-(4-(4-fluorophenyl)-2-(methylsulfinyl)-1H-imidazol-5-yl)pyridin-2-yl)acetamide | 1289617-86-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-fluorophenyl)-N-(4-(4-(4-fluorophenyl)-2-(methylsulfinyl)-1H-imidazol-5-yl)pyridin-2-yl)acetamide
• 英文别名: (S)-2-(4-fluorophenyl)-N-(4-(4-(4-fluorophenyl)-2-(methylsulfinyl)-1H-imidazol-5-yl)pyridin-2-yl)acetamide；2-(4-fluorophenyl)-N-[4-[5-(4-fluorophenyl)-2-[(S)-methylsulfinyl]-1H-imidazol-4-yl]pyridin-2-yl]acetamide
• CAS: 1289617-86-2
• 化学式: C₂₃H₁₈F₂N₄O₂S
• 分子量: 452.484
• InChiKey: CHQVABOBZWQZHI-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(5-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-4-yl)pyridin-2-amine 在 titanium(IV) isopropylate 、 (R)-1,1'-Bi-2-naphthol 、 N,N'-羰基二咪唑 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 水 为溶剂， 反应 2.83h， 生成 2-(4-fluorophenyl)-N-(4-(4-(4-fluorophenyl)-2-(methylsulfinyl)-1H-imidazol-5-yl)pyridin-2-yl)acetamide
  参考文献：
  名称：

  Chiral Sulfoxides as Metabolites of 2-Thioimidazole-Based p38α Mitogen-Activated Protein Kinase Inhibitors: Enantioselective Synthesis and Biological Evaluation

  摘要：

  A number of pharmaceutically important drugs contain asymmetric sulfinyl moieties, so the biological evaluation of chiral sulfoxides as human drug metabolites is important for the development of safe and effective pharmaceuticals. Asymmetric oxidation is one of the most attractive ways to prepare chiral sulfoxides. In combination with different chiral ligands, the iron- and titanium-catalyzed asymmetric oxidations of tri- and tetrasubstituted 2-thioimidazoles afford the corresponding sulfoxides with enantiomeric excesses up to 99% as novel p38a mitogen-activated protein kinase (p38 alpha MAPK) inhibitors. The enantiomerically pure sulfoxides were evaluated on their inhibitory potency against p38 alpha MAPK compared to the respective sulfides and sulfoxide racemates and showed differences in their affinities for the enzyme with IC(50) in the low nanomolar range. In addition, the ability to inhibit the release of tumor necrosis factor-alpha (TNF-alpha) from human whole blood (HWB) was examined. Some pyridinylimidazole derivatives showed excellent HWB activity with IC(50) as low as 52 nM.

  DOI：

  10.1021/jm101623p