3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-2-oxopyridin-1 (2H)-yl]-4-methylbenzoic acid | 586381-87-5

• 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-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-2-oxopyridin-1 (2H)-yl]-4-methylbenzoic acid
• 英文别名: 3-[3-Bromo-4-[(2,4-difluorophenyl)methoxy]-6-(hydroxymethyl)-2-oxopyridin-1-yl]-4-methylbenzoic acid
• CAS: 586381-87-5
• 化学式: C₂₁H₁₆BrF₂NO₅
• 分子量: 480.263
• InChiKey: TYEFIYURUIKFIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 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：
  87.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-2-oxopyridin-1 (2H)-yl]-4-methylbenzoic acid 、 甲胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以65%的产率得到3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-2-oxopyridin-1(2H)-yl]-N,4-dimethylbenzamide
  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
• 作为产物：
  描述：

  Methyl-3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-2-oxopyridin-1(2H)-yl]-4-methylbenzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以90%的产率得到3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-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

• Substituted pyridinones
  申请人：——

  公开号：US20040058964A1

  公开（公告）日：2004-03-25

  Disclosed are compounds Formula I 1 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.

  本发明涉及化合物I1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调节的p38 MAP激酶和/或TNF活性引起或加重的疾病和病况。本发明还涉及含有该化合物的药物组合物、制备该化合物的方法以及使用该化合物进行治疗的方法。
• P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD
  申请人：Fulcrum Therapeutics, Inc.

  公开号：US10342786B2

  公开（公告）日：2019-07-09

  The disclosure relates to methods and compositions including p38 kinase inhibitors and agents that regulate expression of DUX4 and downstream genes including but not restricted to ZSCAN4, LEUTX, PRAMEF2, TRIM43, MBD3L2, KHDC1L, RFPL2, CCNA1, SLC34A2, TPRX1, PRAMEF20, TRIM49, PRAMEF4, PRAME6, PRAMEF15, or ZNF280A. Methods useful for treating a disease associated with abnormal DUX4 and downstream gene expression (e.g., Fascioscapulohumeral muscular dystrophy) are disclosed.

  本发明公开了包括 p38 激酶抑制剂和调节 DUX4 及下游基因（包括但不限于 ZSCAN4、LEUTX、PRAMEF2、TRIM43、MBD3L2、KHDC1L、RFPL2、CCNA1、SLC34A2、TPRX1、PRAMEF20、TRIM49、PRAMEF4、PRAME6、PRAMEF15 或 ZNF280A）表达的制剂在内的方法和组合物。本研究公开了用于治疗与 DUX4 及下游基因表达异常有关的疾病（如筋膜囊性肌营养不良症）的方法。
• SUBSTITUTED PYRIDINONES AS MODULATORS OF P38 MAP KINASE
  申请人：Pharmacia Corporation

  公开号：EP1490064B1

  公开（公告）日：2009-11-18
• P38 KINASE INHIBITORS REDUCE DUX4 AND DOWNSTREAM GENE EXPRESSION FOR THE TREATMENT OF FSHD
  申请人：Fulcrum Therapeutics, Inc.

  公开号：EP3691620A1

  公开（公告）日：2020-08-12
• US7067540B2
  申请人：——

  公开号：US7067540B2

  公开（公告）日：2006-06-27