1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-(methylsulfonyl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)urea | 1160825-41-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-(methylsulfonyl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)urea
• 英文别名: 1-[4-Chloro-3-(trifluoromethyl)phenyl]-3-[2-methylsulfonyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]pyridin-7-yl)oxy]phenyl]urea
• CAS: 1160825-41-1
• 化学式: C₂₁H₁₅ClF₃N₅O₅S
• 分子量: 541.895
• InChiKey: CNGHLWXQLDWOAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-(4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-7-yloxy)-2-(methylthio)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea 在 Oxone 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 以60%的产率得到1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-(methylsulfonyl)-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)urea
  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