2-(4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-ylthio)ethanol | 1061601-11-3

• 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-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-ylthio)ethanol
• 英文别名: 2-(4-(4-Fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-ylthio)-ethanol；2-[[4-(4-fluorophenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]sulfanyl]ethanol
• CAS: 1061601-11-3
• 化学式: C₁₆H₁₄FN₃OS
• 分子量: 315.371
• InChiKey: VGTVABAAMSLUFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 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：
  5

反应信息

• 作为产物：
  描述：

  4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydro-imidazole-2-thione 、 2-溴乙醇 在 potassium tert-butylate 作用下， 以 甲醇 为溶剂， 反应 2.25h， 以40%的产率得到2-(4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-ylthio)ethanol
  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

文献信息

• 2-SUBSTITUTED IMIDAZOLES USEFUL IN THE TREATMENT OF INFLAMMATORY DISEASES
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP0994858A1

  公开（公告）日：2000-04-26
• [EN] 2-SUBSTITUTED IMIDAZOLES USEFUL IN THE TREATMENT OF INFLAMMATORY DISEASES<br/>[FR] IMIDAZOLES SUBSTITUEES EN 2 UTILISABLES POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：ORTHO-McNEIL PHARMACEUTICAL, INC.

  公开号：WO1999003837A1

  公开（公告）日：1999-01-28

  (EN) This invention relates to substituted imidazoles of Formula (I), pharmaceutical compositions containing them, methods of using them and intermediates useful in their manufacture. The compounds of the invention modulate the production of a number of inflammatory cytokines, and are useful in the treatment of diseases associated with the production of inflammatory cytokines.(FR) L'invention porte sur des imidazoles substituées de formule (I), sur des préparations pharmaceutiques les contenant, sur leurs modes d'utilisation, et sur leurs intermédiaires de fabrication. Les composés de l'invention, qui modulent la production de certaines cytokines inflammatoires, servent à traiter les maladies associées à la production desdites cytokines.
• 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
  作者：Pierre Koch、Christiane Bäuerlein、Hartmut Jank、Stefan Laufer

  DOI：10.1021/jm800373t

  日期：2008.9.25

  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.