3-[2-((N-methylsulfamoyl)amino)-3-fluoropyridin-4-ylmethyl]-4-methyl-7-phenoxychromen-2-one | 1548889-68-4

• 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: 3-[2-((N-methylsulfamoyl)amino)-3-fluoropyridin-4-ylmethyl]-4-methyl-7-phenoxychromen-2-one
• 英文别名: 3-[[3-Fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]-4-methyl-7-phenoxychromen-2-one；3-[[3-fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]-4-methyl-7-phenoxychromen-2-one
• CAS: 1548889-68-4
• 化学式: C₂₃H₂₀FN₃O₅S
• 分子量: 469.493
• InChiKey: FXNBBQANCQCLGY-UHFFFAOYSA-N

物化性质

• 沸点：
  636.8±65.0 °C(predicted)
• 密度：
  1.428±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氯-3-氟吡啶 在 吡啶 、 咪唑 、 sodium tetrahydroborate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 硫酸 、 四丁基氟化铵 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 甲基磺酰氯 、 sodium t-butanolate 、 lithium tert-butoxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 23.67h， 生成 3-[2-((N-methylsulfamoyl)amino)-3-fluoropyridin-4-ylmethyl]-4-methyl-7-phenoxychromen-2-one
  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.