methyl 3-(4-((2,4-difluorobenzyl)oxy)-5-ethyl-2-(methylthio)-6-oxopyrimidin-1(6H)-yl)-4-methylbenzoate | 1314804-44-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-(4-((2,4-difluorobenzyl)oxy)-5-ethyl-2-(methylthio)-6-oxopyrimidin-1(6H)-yl)-4-methylbenzoate
• CAS: 1314804-44-8
• 化学式: C₂₃H₂₂F₂N₂O₄S
• 分子量: 460.501
• InChiKey: DEQBSYFHGLHLLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.47
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  70.42
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-((2,4-difluorobenzyl)oxy)-5-ethyl-2-(methylthio)-6-oxopyrimidin-1(6H)-yl)-4-methylbenzoate 在 草酰氯 、 柠檬酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 3-[4-[(2,4-difluorobenzyl)oxy]-5-ethyl-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide
  参考文献：
  名称：

  Substituted N -aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

  摘要：

  A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (> 90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-alpha in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.006
• 作为产物：
  描述：

  methyl 3-[(aminocarbonothioyl)amino]-4-methylbenzoate 在 18-冠醚-6 、 sodium methylate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 methyl 3-(4-((2,4-difluorobenzyl)oxy)-5-ethyl-2-(methylthio)-6-oxopyrimidin-1(6H)-yl)-4-methylbenzoate
  参考文献：
  名称：

  Substituted N -aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

  摘要：

  A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (> 90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-alpha in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.006