methyl-4-[4-[2,4-(difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]benzoate | 586375-22-6

• 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-4-[4-[2,4-(difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]benzoate
• 英文别名: Methyl 4-[4-[(2,4-difluorophenyl)methoxy]-2-methyl-6-oxopyridin-1-yl]benzoate
• CAS: 586375-22-6
• 化学式: C₂₁H₁₇F₂NO₄
• 分子量: 385.367
• InChiKey: QPVFGICBWWJEJY-UHFFFAOYSA-N

物化性质

• 沸点：
  557.4±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl-4-[4-[2,4-(difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]benzoate 在 N-甲基吗啉 、 ammonium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 硼烷四氢呋喃络合物 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 potassium trimethylsilonate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 19.0h， 生成 [2-[[4-[3-Bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]phenyl]methylamino]-2-oxoethyl] acetate
  参考文献：
  名称：

  Design, synthesis and activity of a potent, selective series of N -aryl pyridinone inhibitors of p38 kinase

  摘要：

  A series of N-aryl pyridinone inhibitors of p38 mitogen activated protein (MAP) kinase were designed and prepared based on the screening hit SC-25028 (1) and structural comparisons to VX-745 (5). The focus of the investigation targeted the dependence of potency and metabolic stability on the benzyloxy connectivity, the role of the C-6 position and the substitution pattern on the N-phenyl ring. Further optimization produced the highly selective and potent pyridinones 2 and 3. These inhibitors exhibited activity in both acute and chronic models of inflammation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.120
• 作为产物：
  描述：

  4-甲氨基苯甲酸 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 邻二氯苯 为溶剂， 反应 72.25h， 生成 methyl-4-[4-[2,4-(difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]benzoate
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIDINONES
  [FR] PYRIDINONES SUBSTITUES

  摘要：

  公开号：

  WO2005018557A3

文献信息

• US7629363B2
  申请人：——

  公开号：US7629363B2

  公开（公告）日：2009-12-08
• [EN] SUBSTITUTED PYRIDINONES<br/>[FR] PYRIDINONES SUBSTITUES
  申请人：PHARMACIA CORP

  公开号：WO2005018557A3

  公开（公告）日：2005-08-04
• Design, synthesis and activity of a potent, selective series of N -aryl pyridinone inhibitors of p38 kinase
  作者：Shaun R. Selness、Terri L. Boehm、John K. Walker、Balekudru Devadas、Richard C. Durley、Ravi Kurumbail、Huey Shieh、Li Xing、Michael Hepperle、Paul V. Rucker、Kevin D. Jerome、Alan G. Benson、Laura D. Marrufo、Heather M. Madsen、Jeff Hitchcock、Tom J. Owen、Lance Christie、Michele A. Promo、Brian S. Hickory、Edgardo Alvira、Win Naing、Radhika Blevis-Bal、Rajesh V. Devraj、Dean Messing、John F. Schindler、Jeffrey Hirsch、Matthew Saabye、Sheri Bonar、Elizabeth Webb、Gary Anderson、Joseph B. Monahan

  DOI：10.1016/j.bmcl.2011.04.120

  日期：2011.7

  A series of N-aryl pyridinone inhibitors of p38 mitogen activated protein (MAP) kinase were designed and prepared based on the screening hit SC-25028 (1) and structural comparisons to VX-745 (5). The focus of the investigation targeted the dependence of potency and metabolic stability on the benzyloxy connectivity, the role of the C-6 position and the substitution pattern on the N-phenyl ring. Further optimization produced the highly selective and potent pyridinones 2 and 3. These inhibitors exhibited activity in both acute and chronic models of inflammation. (C) 2011 Elsevier Ltd. All rights reserved.