4-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridine-1(2H)-yl)-N,3-dimethylbenzamide | 586379-41-1

• 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: 4-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridine-1(2H)-yl)-N,3-dimethylbenzamide
• 英文别名: 4-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)-N,3-dimethylbenzamide；4-[3-bromo-4-[(2,4-difluorophenyl)methoxy]-6-methyl-2-oxopyridin-1-yl]-N,3-dimethylbenzamide
• CAS: 586379-41-1
• 化学式: C₂₂H₁₉BrF₂N₂O₃
• 分子量: 477.305
• InChiKey: GKBCRGSJKWXMSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 4-(4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-3-methylbenzoate 在 溴 、 potassium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridine-1(2H)-yl)-N,3-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

文献信息

• 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。
• 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
• [EN] P38 KINASE INHIBITORS REDUCE DUX4 AND DOWNSTREAM GENE EXPRESSION FOR THE TREATMENT OF FSHD<br/>[FR] INHIBITEURS DE LA KINASE P38 RÉDUISANT L'EXPRESSION DU GÈNE DUX4 ET DES GÈNES AVAL POUR LE TRAITEMENT DE LA FSHD
  申请人：FULCRUM THERAPEUTICS INC

  公开号：WO2019071147A1

  公开（公告）日：2019-04-11

  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, KHDClL, RFPL2, CCNAl, SLC34A2, TPRXl, PRAMEF20, TRIM49, PRAMEF4, PRAME6, PRAMEFl5, or ZNF280A. Methods useful for treating a disease associated with abnormal DUX4 and downstream gene expression (e.g., Fascioscapulohumeral muscular dystrophy) are disclosed.
• Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase
  作者：Shaun R. Selness、Rajesh V. Devraj、Balekudru Devadas、John K. Walker、Terri L. Boehm、Richard C. Durley、Huey Shieh、Li Xing、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、Dean Messing、Jerry Yang、Michael K. Mao、Gopi Yalamanchili、Richard Vonder Embse、Jeffrey Hirsch、Matthew Saabye、Sheri Bonar、Elizabeth Webb、Gary Anderson、Joseph B. Monahan

  DOI：10.1016/j.bmcl.2011.04.121

  日期：2011.7

  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.