3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)-N-(1-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzamide | 1213706-75-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)-N-(1-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzamide
• 英文别名: N-[2-(4-methylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]-3-[(2-oxo-1,3-dihydroimidazo[4,5-b]pyridin-7-yl)oxy]benzamide
• CAS: 1213706-75-2
• 化学式: C₂₄H₁₇F₃N₆O₃
• 分子量: 494.433
• InChiKey: CUHOGQQFHPYMAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 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：
  110
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  methyl 3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)benzoate 、 1-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-5-amine 在 三甲基铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 19.0h， 以36%的产率得到3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)-N-(1-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzamide
  参考文献：
  名称：

  BRAF Inhibitors Based on an Imidazo[4,5]pyridin-2-one Scaffold and a Meta Substituted Middle Ring

  摘要：

  We recently reported on the development of a novel series of BRAF inhibitors based on a tripartite A-B-C system characterized by a para-substituted central aromatic core connected to an imidazo-[4,5]pyridin-2-one scaffold and it substituted urea linker. Here, we present it new series of BRAY inhibitors in which the central phenyl ring connects to the hinge binder and substrate pocket of BRAF with a meta-substitution pattern. The optimization of this new scaffold led to the development of low-nanomolar inhibitors that permits the use of a wider range of linkers and terminal C rings while enhancing the selectivity for the BRAF enzyme in comparison to the para series.

  DOI：

  10.1021/jm901509a

文献信息

• BRAF Inhibitors Based on an Imidazo[4,5]pyridin-2-one Scaffold and a Meta Substituted Middle Ring
  作者：Arnaud Nourry、Alfonso Zambon、Lawrence Davies、Ion Niculescu-Duvaz、Harmen P. Dijkstra、Delphine Ménard、Catherine Gaulon、Dan Niculescu-Duvaz、Bart M. J. M. Suijkerbuijk、Frank Friedlos、Helen A. Manne、Ruth Kirk、Steven Whittaker、Richard Marais、Caroline J. Springer

  DOI：10.1021/jm901509a

  日期：2010.3.11

  We recently reported on the development of a novel series of BRAF inhibitors based on a tripartite A-B-C system characterized by a para-substituted central aromatic core connected to an imidazo-[4,5]pyridin-2-one scaffold and it substituted urea linker. Here, we present it new series of BRAY inhibitors in which the central phenyl ring connects to the hinge binder and substrate pocket of BRAF with a meta-substitution pattern. The optimization of this new scaffold led to the development of low-nanomolar inhibitors that permits the use of a wider range of linkers and terminal C rings while enhancing the selectivity for the BRAF enzyme in comparison to the para series.