dimethyl-carbamic acid 3-[(5-((N-methylsulfamoyl)amino)pyridin-3-yl)methyl]-4-methyl-2-oxo-2H-chromen-7-yl ester | 1548889-61-7

• 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
• 英文名称: dimethyl-carbamic acid 3-[(5-((N-methylsulfamoyl)amino)pyridin-3-yl)methyl]-4-methyl-2-oxo-2H-chromen-7-yl ester
• 英文别名: [4-methyl-3-[[5-(methylsulfamoylamino)pyridin-3-yl]methyl]-2-oxochromen-7-yl] N,N-dimethylcarbamate
• CAS: 1548889-61-7
• 化学式: C₂₀H₂₂N₄O₆S
• 分子量: 446.484
• InChiKey: NOZUCNQJIWADAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 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 、 三乙胺 作用下， 以 四氢呋喃 、 四氯化碳 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 63.83h， 生成 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

文献信息

• Optimizing the Physicochemical Properties of Raf/MEK Inhibitors by Nitrogen Scanning
  作者：Toshihiro Aoki、Ikumi Hyohdoh、Noriyuki Furuichi、Sawako Ozawa、Fumio Watanabe、Masayuki Matsushita、Masahiro Sakaitani、Kenji Morikami、Kenji Takanashi、Naoki Harada、Yasushi Tomii、Koji Shiraki、Kentaro Furumoto、Mitsuyasu Tabo、Kiyoshi Yoshinari、Kazutomo Ori、Yuko Aoki、Nobuo Shimma、Hitoshi Iikura

  DOI：10.1021/ml400379x

  日期：2014.4.10

  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.