ethyl 2-[(4-{bis[(tert-butoxy)carbonyl]amino}pyridin-2-yl)methyl]-3-oxobutanoate | 1548889-11-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: ethyl 2-[(4-{bis[(tert-butoxy)carbonyl]amino}pyridin-2-yl)methyl]-3-oxobutanoate
• 英文别名: ethyl 2-[[4-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]pyridin-2-yl]methyl]-3-oxobutanoate
• CAS: 1548889-11-7
• 化学式: C₂₂H₃₂N₂O₇
• 分子量: 436.505
• InChiKey: JDXDLTCFDHLBHX-UHFFFAOYSA-N

物化性质

• 沸点：
  511.5±60.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 2-[(4-{bis[(tert-butoxy)carbonyl]amino}pyridin-2-yl)methyl]-3-oxobutanoate 在 硫酸 、 potassium carbonate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 29.08h， 生成 dimethyl-carbamic acid 3-[4-(N-methylsulfamoylamino)pyridin-2-ylmethyl]-4,6-dimethyl-2-oxo-2H-chromen-7-yl ester
  参考文献：
  名称：

  Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning

  摘要：

  Substituting a carbon atom with a nitrogen atom (nitrogen substitution) on an aromatic ring in our leads 1 la and 13g by applying nitrogen scanning afforded a set of compounds that improved not only the solubility but also the metabolic stability. The impact after nitrogen substitution on interactions between a derivative and its on- and off-target proteins (Raf/MEK, CYPs, and hERG channel) was also detected, most of them contributing to weaker interactions. After identifying the positions that kept inhibitory activity on HCT116 cell growth and Raf/MEK, compound I (CH5126766/RO5126766) was selected as a clinical compound. A phase I clinical trial is ongoing for solid cancers.

  DOI：

  10.1021/ml400379x
• 作为产物：
  描述：

  (2-methylpyridin-4-yl)carbamic acid tert-butyl ester 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 sodium hydride 作用下， 以 四氢呋喃 、 四氯化碳 、 mineral oil 为溶剂， 反应 31.75h， 生成 ethyl 2-[(4-{bis[(tert-butoxy)carbonyl]amino}pyridin-2-yl)methyl]-3-oxobutanoate
  参考文献：
  名称：

  Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning

  摘要：

  Substituting a carbon atom with a nitrogen atom (nitrogen substitution) on an aromatic ring in our leads 1 la and 13g by applying nitrogen scanning afforded a set of compounds that improved not only the solubility but also the metabolic stability. The impact after nitrogen substitution on interactions between a derivative and its on- and off-target proteins (Raf/MEK, CYPs, and hERG channel) was also detected, most of them contributing to weaker interactions. After identifying the positions that kept inhibitory activity on HCT116 cell growth and Raf/MEK, compound I (CH5126766/RO5126766) was selected as a clinical compound. A phase I clinical trial is ongoing for solid cancers.

  DOI：

  10.1021/ml400379x