3-[4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid | 773104-06-6

• 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: 3-[4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid
• 英文别名: 3-[4-[(2,4-difluorophenyl)methoxy]-6-oxopyrimidin-1-yl]-4-methylbenzoic acid
• CAS: 773104-06-6
• 化学式: C₁₉H₁₄F₂N₂O₄
• 分子量: 372.328
• InChiKey: PNYVFUMHNPBYTE-UHFFFAOYSA-N

物化性质

• 沸点：
  583.2±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid 在 N-甲基吗啉 、 二氯乙酸 、 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基乙酰胺 、 1,2-二氯乙烷 为溶剂， 生成 N-[(1R)-1-(aminocarbonyl)ethyl]-3-[5-chloro-4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]-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：

  3-氨基-4-甲基苯甲酸甲酯 在 sodium methylate 、 potassium carbonate 、 柠檬酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N-甲基吡咯烷酮 、 N,N-二甲基乙酰胺 为溶剂， 反应 33.0h， 生成 3-[4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid
  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

文献信息

• Substituted pyrimidinones
  申请人：——

  公开号：US20040242608A1

  公开（公告）日：2004-12-02

  Disclosed are compounds Formula I 1 and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 4 , and R 5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.

  本发明涉及化合物I1及其药学上可接受的盐，其中R1、R2、R4和R5的定义如下。这些化合物可用于治疗由未调节的p38 MAP激酶和/或TNF活性引起或恶化的疾病和病况。本发明还涉及含有这些化合物的药物组合物、制备这些化合物的方法以及使用这些化合物进行治疗的方法。
• SUBSTITUTED PYRIMIDINONES
  申请人：Durley C. Richard

  公开号：US20070167621A1

  公开（公告）日：2007-07-19

  Disclosed are compounds Formula I and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 4 , and R 5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.

  本发明涉及化合物I的公式及其药学上可接受的盐，其中R1、R2、R4和R5在此定义。这些化合物可用于治疗由未经调节的p38 MAP激酶和/或TNF活性引起或恶化的疾病和病况。本发明还涉及含有这些化合物的药物组合物、制备这些化合物的方法以及使用这些化合物的治疗方法。
• PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS P38 KINASE MODULATORS
  申请人：Pharmacia Corporation

  公开号：EP1753731A2

  公开（公告）日：2007-02-21
• US7183287B2
  申请人：——

  公开号：US7183287B2

  公开（公告）日：2007-02-27
• US7795271B2
  申请人：——

  公开号：US7795271B2

  公开（公告）日：2010-09-14