1-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid | 821791-26-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid
• 英文别名: 1-[3-[Tert-butyl(dimethyl)silyl]oxypropyl]-4-(2-fluoro-4-iodoanilino)-6-oxopyridine-3-carboxylic acid
• CAS: 821791-26-8
• 化学式: C₂₁H₂₈FIN₂O₄Si
• 分子量: 546.453
• InChiKey: FAAZTYLWIPRFPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.45
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  吡啶 、 1-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid 、 三氟乙酸五氟苯酯 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  4-Anilino-5-carboxamido-2-pyridone Derivatives as Noncompetitive Inhibitors of Mitogen-Activated Protein Kinase Kinase

  摘要：

  A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by supression of phosphorylated ERK, substrate. Most notably, pyridone 27 was found to be more potent than I in vitro and produced a 100% response rate at a lower dose than 1, when tested for in vivo efficacy in animals bearing C26 tumors.

  DOI：

  10.1021/jm0704548
• 作为产物：
  描述：

  ethyl 4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxylate 、 (3-溴丙氧基)叔丁基二甲基硅烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 以34%的产率得到1-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-4-(2-fluoro-4-iodoanilino)-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid
  参考文献：
  名称：

  4-Anilino-5-carboxamido-2-pyridone Derivatives as Noncompetitive Inhibitors of Mitogen-Activated Protein Kinase Kinase

  摘要：

  A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by supression of phosphorylated ERK, substrate. Most notably, pyridone 27 was found to be more potent than I in vitro and produced a 100% response rate at a lower dose than 1, when tested for in vivo efficacy in animals bearing C26 tumors.

  DOI：

  10.1021/jm0704548