3-(5-bromo-4-((2,4-difluorobenzyl)oxy)-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid | 586379-64-8

• 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: 3-(5-bromo-4-((2,4-difluorobenzyl)oxy)-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid
• 英文别名: 3-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid；3-[3-bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]-4-methylbenzoic acid
• CAS: 586379-64-8
• 化学式: C₂₁H₁₆BrF₂NO₄
• 分子量: 464.263
• InChiKey: GPZOARIYKKLIHM-UHFFFAOYSA-N

物化性质

• 沸点：
  616.6±55.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(5-bromo-4-((2,4-difluorobenzyl)oxy)-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid 生成 3-[3-Bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]-4-methylbenzoyl chloride
  参考文献：
  名称：

  Processes for the preparation of 3-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)-N,4-dimethylbenzamide

  摘要：

  本发明通常涉及制备公式I化合物的过程：其中R2、R3、R4、R5、X1、X2、X3、X4、X5、X6如规范中所定义。

  公开号：

  US07906536B2
• 作为产物：
  描述：

  3-氨基-4-甲基苯甲酸甲酯 在 溴 、 potassium carbonate 、 溶剂黄146 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 邻二氯苯 为溶剂， 生成 3-(5-bromo-4-((2,4-difluorobenzyl)oxy)-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid
  参考文献：
  名称：

  Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase

  摘要：

  The synthesis and SAR studies of a novel N-aryl pyridinone class of p38 kinase inhibitors are described. Systematic structural modifications to the HTS lead, 5, led to the identification of (-)-4a as a clinical candidate for the treatment of inflammatory diseases. Additionally, the chiral synthesis and properties of (-)-4a are described. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.121

文献信息

• Optimal linker length for small molecule PROTACs that selectively target p38α and p38β for degradation
  作者：Craig Donoghue、Monica Cubillos-Rojas、Nuria Gutierrez-Prat、Carolina Sanchez-Zarzalejo、Xavier Verdaguer、Antoni Riera、Angel R. Nebreda

  DOI：10.1016/j.ejmech.2020.112451

  日期：2020.9

  p38β for degradation. These proteolysis targeted chimeras (PROTACs) are based on an ATP competitive inhibitor of p38α and p38β, which is linked to thalidomide analogues to recruit the Cereblon E3 ubiquitin ligase complex. Compound synthesis was facilitated by the use of a copper catalyzed “click” reaction. We show that optimization of the linker length and composition is crucial for the degradation-inducing

  我们报道了选择性靶向p38α和p38β降解的异双功能小分子的设计。这些靶向蛋白质水解的嵌合体（PROTAC）基于p38α和p38β的ATP竞争性抑制剂，后者与沙利度胺类似物相连以募集Cereblon E3泛素连接酶复合物。通过使用铜催化的“喀哒”反应可促进化合物的合成。我们表明，优化连接子的长度和组成对于这些PROTAC的降解诱导活性至关重要。我们提供的证据表明，这些化合物可以诱导p38α和p38β的降解，但是在几种哺乳动物细胞系中，在纳摩尔浓度下没有其他相关的激酶。因此，PROTACs抑制压力和细胞因子诱导的p38α信号传导。我们的化合物有助于理解PROTAC的发展，
• Substituted pyridinones
  申请人：Devadas Balekudru

  公开号：US20050176775A1

  公开（公告）日：2005-08-11

  Disclosed are compounds of Formula I and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , 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.

  本发明涉及式I的化合物及其药学上可接受的盐，其中R1、R2、R3、R4和R5在此被定义。这些化合物可用于治疗由未调节的p38 MAP激酶和/或TNF活性引起或加剧的疾病和状况。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。
• PROCESSES FOR THE PREPARATION OF 3-(4-(2,4-DIFLUOROBENZYLOXY)-3-BROMO-6-METHYL-2-OXOPYRIDIN-1(2H)-YL)-N,4-DIMETHYLBENZAMIDE
  申请人：Dukesherer Daniel

  公开号：US20080177077A1

  公开（公告）日：2008-07-24

  This invention is directed generally to processes for the preparation of compounds of Formula I: wherein R 2 , R 3 , R 4 , R 5 , X 1 , X 2 , X 3 , X 4 , X 5 , X 6 are as defined in the specification.

  本发明通常涉及制备式I化合物的过程：其中R2、R3、R4、R5、X1、X2、X3、X4、X5、X6如规范中所定义。
• Diaryl substituted pyridinones
  申请人：Pfizer Inc

  公开号：US07629363B2

  公开（公告）日：2009-12-08

  Disclosed are compounds Formula I and pharmaceutically acceptable salts thereof, wherein R1, R2, R3/R4, and R5 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的公开式及其药学上可接受的盐，其中R1、R2、R3/R4和R5的定义如下。这些化合物可用于治疗由未受调节的p38 MAP激酶和/或TNF活性引起或恶化的疾病和病况。本发明还公开了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。
• WO2008/72079
  申请人：——

  公开号：——

  公开（公告）日：——