N-cyclohexyl-4-(4-(4-fluorophenyl)-2-(isopropylthio)-1H-imidazol-5-yl)pyridin-2-amine | 1289616-87-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-cyclohexyl-4-(4-(4-fluorophenyl)-2-(isopropylthio)-1H-imidazol-5-yl)pyridin-2-amine
• 英文别名: N-Cyclohexyl-4-(4-(4-fluorophenyl)-2-(isopropylthio)-1Himidazol-5-yl)pyridin-2-amine；N-cyclohexyl-4-[5-(4-fluorophenyl)-2-propan-2-ylsulfanyl-1H-imidazol-4-yl]pyridin-2-amine
• CAS: 1289616-87-0
• 化学式: C₂₃H₂₇FN₄S
• 分子量: 410.559
• InChiKey: KAKPVALXSVEUNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-cyclohexyl-4-(4-(4-fluorophenyl)-2-(isopropylthio)-1H-imidazol-5-yl)pyridin-2-amine 在 potassium peroxomonosulfate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.5h， 以65.8%的产率得到N-cyclohexyl-4-(4-(4-fluorophenyl)-2-(isopropylsulfinyl)-1H-imidazol-5-yl)pyridin-2-amine
  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
• 作为产物：
  描述：

  4-(4-氟苯基)-5-(2-氟吡啶-4-基)-1,3-二氢咪唑-2-硫酮 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 36.0h， 生成 N-cyclohexyl-4-(4-(4-fluorophenyl)-2-(isopropylthio)-1H-imidazol-5-yl)pyridin-2-amine
  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

文献信息

• 2-Thio-substituted imidazole derivatives and their use in pharmaceutics
  申请人：Laufer Stefan

  公开号：US20060235054A1

  公开（公告）日：2006-10-19

  The invention relates to 2-thio-substituted imidazole derivatives of the formula I in which the radicals R 1 , R 2 R 3 and m are as defined in the description. The compounds according to the invention have immunomodulating and/or cytokine-release-inhibiting action and are therefore suitable for treating disorders associated with a disturbed immune system.

  本发明涉及公式I中的2-硫代取代咪唑衍生物，其中基团R1，R2，R3和m如描述中所定义。本发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统紊乱相关的疾病。
• US7582660B2
  申请人：——

  公开号：US7582660B2

  公开（公告）日：2009-09-01
• Chiral Sulfoxides as Metabolites of 2-Thioimidazole-Based p38α Mitogen-Activated Protein Kinase Inhibitors: Enantioselective Synthesis and Biological Evaluation
  作者：Stefanie Bühler、Marcia Goettert、Dieter Schollmeyer、Wolfgang Albrecht、Stefan A. Laufer

  DOI：10.1021/jm101623p

  日期：2011.5.12

  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.