N-[2-(4-fluorobenzoyl)phenyl]-2-pyridin-4-ylacetamide | 1026902-78-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[2-(4-fluorobenzoyl)phenyl]-2-pyridin-4-ylacetamide
• CAS: 1026902-78-2
• 化学式: C₂₀H₁₅FN₂O₂
• 分子量: 334.35
• InChiKey: DEWQTEFEUDCCLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  59.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[2-(4-fluorobenzoyl)phenyl]-2-pyridin-4-ylacetamide 在 ammonium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-(4-Fluorophenyl)-3-(pyridin-4-yl)quinolin-2(1H)-one
  参考文献：
  名称：

  From Five- to Six-Membered Rings:  3,4-Diarylquinolinone as Lead for Novel p38MAP Kinase Inhibitors

  摘要：

  In this study we describe the design, synthesis, and biological evaluation of 3-(4-fluorophenyl)-4-pyridin-4-ylquinoline-2(1H)-one (5) as a new inhibitor of MAPK with a p38 alpha MAPK IC50 of 1.8 mu M. By keeping the common vicinal pyridine/4-F-phenyl pharmacophore, such as in prototypical imidazole 20 or isoxazole 13 but in 5 connected to the six-membered quinoline core, we were particularly interested in comparing biological activity, details of molecular geometry, and different binding modes of these compounds. Compounds 20 and 13 were active both in the p38 alpha- and JNK3-assay, whereas 5 was selective for p38 alpha, with no JNK3 inhibition. By comparing the X-ray structures of the compounds, we found a significantly larger distance between the pyridine and the 4-F-phenyl moiety in five-membered core structures relevant for ligand-protein interactions. Molecular modeling studies support the results based on differences in the ATP pockets of p38 alpha and JNK3. Because most five-membered core based p38 alpha inhibitors show also activity for JNK3, compound 5 is an interesting lead for selective p38 alpha inhibitors.

  DOI：

  10.1021/jm061097o
• 作为产物：
  描述：

  2-{[(4-甲基苯基)磺酰基]氨基}苯甲酸 在 盐酸 、 五氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 生成 N-[2-(4-fluorobenzoyl)phenyl]-2-pyridin-4-ylacetamide
  参考文献：
  名称：

  From Five- to Six-Membered Rings:  3,4-Diarylquinolinone as Lead for Novel p38MAP Kinase Inhibitors

  摘要：

  In this study we describe the design, synthesis, and biological evaluation of 3-(4-fluorophenyl)-4-pyridin-4-ylquinoline-2(1H)-one (5) as a new inhibitor of MAPK with a p38 alpha MAPK IC50 of 1.8 mu M. By keeping the common vicinal pyridine/4-F-phenyl pharmacophore, such as in prototypical imidazole 20 or isoxazole 13 but in 5 connected to the six-membered quinoline core, we were particularly interested in comparing biological activity, details of molecular geometry, and different binding modes of these compounds. Compounds 20 and 13 were active both in the p38 alpha- and JNK3-assay, whereas 5 was selective for p38 alpha, with no JNK3 inhibition. By comparing the X-ray structures of the compounds, we found a significantly larger distance between the pyridine and the 4-F-phenyl moiety in five-membered core structures relevant for ligand-protein interactions. Molecular modeling studies support the results based on differences in the ATP pockets of p38 alpha and JNK3. Because most five-membered core based p38 alpha inhibitors show also activity for JNK3, compound 5 is an interesting lead for selective p38 alpha inhibitors.

  DOI：

  10.1021/jm061097o