dimethyl-carbamic acid 3-((5-amino-pyridin-3-yl)methyl)-4-methyl-2-oxo-2H-chromen-7-yl ester | 1548890-04-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: dimethyl-carbamic acid 3-((5-amino-pyridin-3-yl)methyl)-4-methyl-2-oxo-2H-chromen-7-yl ester
• CAS: 1548890-04-5
• 化学式: C₁₉H₁₉N₃O₄
• 分子量: 353.378
• InChiKey: OJFPNLGKZVIJIP-UHFFFAOYSA-N

物化性质

• 沸点：
  596.1±50.0 °C(predicted)
• 密度：
  1.317±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  98.66
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-甲基-2-氧代-1,3-恶唑烷-3-磺酰胺 、 dimethyl-carbamic acid 3-((5-amino-pyridin-3-yl)methyl)-4-methyl-2-oxo-2H-chromen-7-yl ester 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以56%的产率得到dimethyl-carbamic acid 3-[(5-((N-methylsulfamoyl)amino)pyridin-3-yl)methyl]-4-methyl-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：

  3-氨基-5-甲基吡啶 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 硫酸 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 四氯化碳 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 57.83h， 生成 dimethyl-carbamic acid 3-((5-amino-pyridin-3-yl)methyl)-4-methyl-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