4-((2,4-difluorobenzyl)oxy)-1-(4-methoxybenzyl)-6-methylpyridin-2(1H)-one | 586375-30-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-((2,4-difluorobenzyl)oxy)-1-(4-methoxybenzyl)-6-methylpyridin-2(1H)-one
• 英文别名: 4-[(2,4-difluorobenzyl)oxy]-1-(4-methoxybenzyl)-6-methylpyridin-2-(1H)-one；4-[(2,4-Difluorophenyl)methoxy]-1-[(4-methoxyphenyl)methyl]-6-methylpyridin-2-one
• CAS: 586375-30-6
• 化学式: C₂₁H₁₉F₂NO₃
• 分子量: 371.384
• InChiKey: DLHASOKUZQDKQO-UHFFFAOYSA-N

物化性质

• 沸点：
  563.5±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-((2,4-difluorobenzyl)oxy)-1-(4-methoxybenzyl)-6-methylpyridin-2(1H)-one 在 N-溴代丁二酰亚胺(NBS) 、 ammonium cerium(IV) nitrate 作用下， 以 水 、 乙腈 为溶剂， 反应 2.0h， 生成 3-bromo-4-[(2,4-difluorobenzyl)oxy]-1-(4-hydroxybenzyl)-6-methylpyridin-2(1H)-one
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIDINONES
  [FR] PYRIDINONES SUBSTITUES

  摘要：

  公开号：

  WO2005018557A3
• 作为产物：
  描述：

  4-甲氧基苄胺 在 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 4-((2,4-difluorobenzyl)oxy)-1-(4-methoxybenzyl)-6-methylpyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of Multitarget Antivirals Acting on Both the Dengue Virus NS5-NS3 Interaction and the Host Src/Fyn Kinases

  摘要：

  This study describes the discovery of novel dengue virus inhibitors targeting both a crucial viral protein protein interaction and an essential host cell factor as a strategy to reduce the emergence of drug resistance. Starting from known c-Src inhibitors, a virtual screening was performed to identify molecules able to interact with a recently discovered allosteric pocket on the dengue virus NS5 polymerase. The selection of cheap-to-produce scaffolds and the exploration of the biologically relevant chemical space around them suggested promising candidates for chemical synthesis. A series of purines emerged as the most interesting candidates able to inhibit virus replication at low micromolar concentrations with no Significant toxicity to the host cell. Among the identified antivirals, compound 16i proved to be 10 times More potent than ribavirin, showed a better selectivity index and represents the first-in-class DENV-NS5 allosteric inhibitor able to target both the virus NS5-NS3 interaction and the host kinases c-Src/Fyn.

  DOI：

  10.1021/acs.jmedchem.5b00108

文献信息

• 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。
• 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