2-(4-(4-fluorphenyl)-5-(2-fluorpyridin-4-yl)-1H-imidazol-2-ylthio)ethanol | 1061602-00-3

• 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-(4-fluorphenyl)-5-(2-fluorpyridin-4-yl)-1H-imidazol-2-ylthio)ethanol
• 英文别名: 2-(4-(4-fluorophenyl)-5-(2-fluoropyridin-4-yl)-1H-imidazol-2-ylthio)ethanol；2-[[5-(4-fluorophenyl)-4-(2-fluoropyridin-4-yl)-1H-imidazol-2-yl]sulfanyl]ethanol
• CAS: 1061602-00-3
• 化学式: C₁₆H₁₃F₂N₃OS
• 分子量: 333.362
• InChiKey: MIFRVKOCORRQSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-(4-fluorphenyl)-5-(2-fluorpyridin-4-yl)-1H-imidazol-2-ylthio)ethanol 、 trans-4-Aminocyclohexanol 反应 3.5h， 以40%的产率得到(1R,4R)-4-(4-(4-(4-fluorophenyl)-2-(2-hydroxyethylthio)-1H-imidazol-5-yl)pyridin-2-ylamino)cyclohexanol
  参考文献：
  名称：

  Targeting the Ribose and Phosphate Binding Site of p38 Mitogen-Activated Protein (MAP) Kinase: Synthesis and Biological Testing of 2-Alkylsulfanyl-, 4(5)-Aryl-, 5(4)-Heteroaryl-Substituted Imidazoles

  摘要：

  Three series of substituted 2-alkylsulfanyl-4-(4-fluorophenyl)imidazoles, 5-pyridinyl-, 1-methyl-5-pyridinyl-, and 5-(2-aminopyridin-4-yl)-imidazoles, were prepared and tested for their ability to inhibit p38 MAP kinase and TNF-alpha release. These compounds were prepared by using different synthetic routes. They were tested by applying a nonradioactive p38 MAP kinase assay and by measurement of TNF-a release in human whole blood. Potent inhibitors (IC(50)values in the low nanomolar range, as low as 2 nM in the enzyme assay and 37 nM in the human whole blood test) were identified by variation of substituents at the imidazole-C2-thio position as well as at the 2-aminopyridinyl functionality. In contrast to other known kinase inhibitors, these novel imidazole derivatives with the substituents at the imidazole-C2-thio position may interact with the ribose as well as with the phosphate binding site of the p38 MAP kinase.

  DOI：

  10.1021/jm800373t
• 作为产物：
  描述：

  1-(2-fluoropyridin-4-yl)-2-(4-fluorophenyl)ethane-1,2-dione 1-oxime 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 sodium ethanolate 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 5.5h， 生成 2-(4-(4-fluorphenyl)-5-(2-fluorpyridin-4-yl)-1H-imidazol-2-ylthio)ethanol
  参考文献：
  名称：

  An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors

  摘要：

  报道了一种针对制备强效吡啶基咪唑类p38α MAP激酶抑制剂的优化和多样化合成方法。

  DOI：

  10.1039/c5ob01505g

文献信息

• KINASE MODULATORS FOR THE TREATMENT OF CANCER
  申请人：Synovo GmbH

  公开号：US20170313661A1

  公开（公告）日：2017-11-02

  A method of treating cancer in which a compound that inhibits the expression, production or release of IL-10 by immune cells is combined with a compound that stimulates the production of IL-12 when given in combination with, or in the presence of TNFa. Said method is effective when provided in addition to standard therapies, notably chemotherapy using cytotoxic drugs and other forms of immune therapy including therapeutic vaccines.

  一种治疗癌症的方法，其中抑制免疫细胞表达、产生或释放IL-10的化合物与在与TNFa联合给予或存在的情况下刺激IL-12产生的化合物结合。所述方法在提供标准疗法的基础上有效，特别是包括使用细胞毒性药物的化疗和其他形式的免疫疗法，包括治疗性疫苗。
• 2-SULFANYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS
  申请人：Burnet Michael

  公开号：US20090270462A1

  公开（公告）日：2009-10-29

  The invention relates to 2-thio-substituted imidazole derivatives of the Formula I, and to methods of use thereof.

  这项发明涉及到式I的2-硫代咪唑衍生物，以及其使用方法。
• Unexpected Reaction of 2-Alkylsulfanylimidazoles to Imidazol-2-ones: Pyridinylimidazol-2-ones as Novel Potent p38α Mitogen-Activated Protein Kinase Inhibitors
  作者：Pierre Koch、Stefan Laufer

  DOI：10.1021/jm100161q

  日期：2010.6.24

  While optimizing the synthesis of 2-alkylsulfanyl-5-(2-aminopyridin-4-yl)imidazoles, we identified an unexpected reaction to pyridinylimidazol-2-ones. 2-Alkylsulfanylimidazoles, bearing a 2-hydroxyethyl or a 2,3-dihydroxypropyl moiety at the imidazole C2-S position, were converted by heating into imidazol-2-ones. These imidazol-2-ones were tested for their ability to inhibit p38 alpha MAP kinase and LPS-stimulated TNF-alpha release in HWB. Introduction of an amino moiety at the pyridine C2 position led to compounds showing potent enzyme inhibitory activity with double-digit nanomolar IC50 values (5a: IC50 = 23 nM).
• US8143294B2
  申请人：——

  公开号：US8143294B2

  公开（公告）日：2012-03-27
• US9617221B2
  申请人：——

  公开号：US9617221B2

  公开（公告）日：2017-04-11