| 1548890-14-7

• 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
• CAS: 1548890-14-7
• 化学式: C₂HF₃O₂*C₂₀H₂₁N₃O₄
• 分子量: 481.428
• InChiKey: ONQQTMAXDLOOMU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  136.69
• 氢给体数：
  3.0
• 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 、 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以69%的产率得到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 、 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 54.83h， 生成
  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