diethyl 2-(4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-ylthio)malonate | 627080-52-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: diethyl 2-(4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-ylthio)malonate
• 英文别名: Diethyl 2-4(4-(4-Fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-ylthio)malonate；diethyl 2-[[4-(4-fluorophenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]sulfanyl]propanedioate
• CAS: 627080-52-8
• 化学式: C₂₁H₂₀FN₃O₄S
• 分子量: 429.472
• InChiKey: UQBINMGQFGILLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydro-imidazole-2-thione 、 溴代丙二酸二乙酯 在 potassium tert-butylate 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以10%的产率得到diethyl 2-(4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-ylthio)malonate
  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

• US7442713B2
  申请人：——

  公开号：US7442713B2

  公开（公告）日：2008-10-28