N-[4-[(1-methyl-2-oxo-3H-imidazo[4,5-b]pyridin-7-yl)oxy]naphthalen-1-yl]-3-(trifluoromethylsulfanyl)benzamide | 1160825-64-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[4-[(1-methyl-2-oxo-3H-imidazo[4,5-b]pyridin-7-yl)oxy]naphthalen-1-yl]-3-(trifluoromethylsulfanyl)benzamide
• CAS: 1160825-64-8
• 化学式: C₂₅H₁₇F₃N₄O₃S
• 分子量: 510.496
• InChiKey: CEYIUMPCOYXIFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-((4-aminonaphthalen-1-yl)oxy)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one 、 3-(trifluoromethylthio)benzoyl chloride 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 20.0h， 以44%的产率得到N-[4-[(1-methyl-2-oxo-3H-imidazo[4,5-b]pyridin-7-yl)oxy]naphthalen-1-yl]-3-(trifluoromethylsulfanyl)benzamide
  参考文献：
  名称：

  Novel Potent BRAF Inhibitors: Toward 1 nM Compounds through Optimization of the Central Phenyl Ring

  摘要：

  BRAF, a serine/threonine specific protein kinase that is part of the MAPK pathway and acts as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have developed a series of small-molecule BRAF inhibitors based on a 1H-imidazo[4,5-b]pyridine-2(3H)-one scaffold (ring A) as the hinge binding moiety and a number Of Substituted phenyl rings C that interact with the allosteric binding site. The introduction of various groups on the central phenyl ring B combined with appropriate A- and C-ring modifications afford very potent compounds that inhibit (V600E)BRAF kinase activity in vitro and oncogqnic BRAF signaling in melanoma cells. Substitution on the central phenyl ring of a 3-fluoro, a naphthyl, or a 3-thiomethyl group improves activity to yield compounds with an IC50 of 1 nM for purified (V600E)BRAF and nanomolar activity in cells.

  DOI：

  10.1021/jm900242c