4-methyl-3-(3-(pyrimidin-4-yl)pyridin-2-yloxy)benzoic acid | 926277-91-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-methyl-3-(3-(pyrimidin-4-yl)pyridin-2-yloxy)benzoic acid
• 英文别名: 4-Methyl-3-(3-pyrimidin-4-ylpyridin-2-yl)oxybenzoic acid
• CAS: 926277-91-0
• 化学式: C₁₇H₁₃N₃O₃
• 分子量: 307.309
• InChiKey: WOOLLPBODHCCJZ-UHFFFAOYSA-N

物化性质

• 沸点：
  531.4±50.0 °C(Predicted)
• 密度：
  1.314±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  85.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-methyl-3-(3-(pyrimidin-4-yl)pyridin-2-yloxy)benzoic acid 、 2-哌啶-1-基-5-(三氟甲基)苯胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以58%的产率得到4-methyl-N-(2-(1-piperidinyl)-5-(trifluoromethyl)phenyl)-3-((3-(4-pyrimidinyl)-2-pyridinyl)oxy)benzamide
  参考文献：
  名称：

  Evolution of a Highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor

  摘要：

  Inhibition of angiogenesis is a promising and clinically validated approach for limiting tumor growth and survival. The receptor tyrosine kinase Tie-2 is expressed almost exclusively in the vascular endothelium and is required for developmental angiogenesis and vessel maturation. However, the significance of Tie-2 signaling in tumor angiogenesis is not well understood. In order to evaluate the therapeutic utility of inhibiting Tie-2 signaling, we developed a series of potent and orally bioavailable small molecule Tie-2 kinase inhibitors with selectivity over other kinases, especially those that are believed to be important for tumor angiogenesis. Our earlier work provided pyridinyl pyrimidine 6 as a potent, nonselective Tie-2 inhibitor that was designed on the basis of X-ray cocrystal structures of KDR inhibitors 34 (triazine) and 35 (nicotinamide). Lead optimization resulted in pyridinyl triazine 63, which exhibited > 30-fold selectivity over a panel of kinases, good oral exposure, and in vivo inhibition of Tie-2 phosphorylation.

  DOI：

  10.1021/jm061107l
• 作为产物：
  描述：

  3-乙酰基-2-氯吡啶 在 sodium methylate 、 caesium carbonate 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 17.67h， 生成 4-methyl-3-(3-(pyrimidin-4-yl)pyridin-2-yloxy)benzoic acid
  参考文献：
  名称：

  Evolution of a Highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor

  摘要：

  Inhibition of angiogenesis is a promising and clinically validated approach for limiting tumor growth and survival. The receptor tyrosine kinase Tie-2 is expressed almost exclusively in the vascular endothelium and is required for developmental angiogenesis and vessel maturation. However, the significance of Tie-2 signaling in tumor angiogenesis is not well understood. In order to evaluate the therapeutic utility of inhibiting Tie-2 signaling, we developed a series of potent and orally bioavailable small molecule Tie-2 kinase inhibitors with selectivity over other kinases, especially those that are believed to be important for tumor angiogenesis. Our earlier work provided pyridinyl pyrimidine 6 as a potent, nonselective Tie-2 inhibitor that was designed on the basis of X-ray cocrystal structures of KDR inhibitors 34 (triazine) and 35 (nicotinamide). Lead optimization resulted in pyridinyl triazine 63, which exhibited > 30-fold selectivity over a panel of kinases, good oral exposure, and in vivo inhibition of Tie-2 phosphorylation.

  DOI：

  10.1021/jm061107l