5-amino-1-(2,5-difluorophenyl)-1H-pyrazole-4-carbaldehyde | 1220512-64-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-1-(2,5-difluorophenyl)-1H-pyrazole-4-carbaldehyde
• 英文别名: 5-Amino-1-(2,5-difluorophenyl)-1H-pyrazole-4-carboxaldehyde；5-amino-1-(2,5-difluorophenyl)pyrazole-4-carbaldehyde
• CAS: 1220512-64-0
• 化学式: C₁₀H₇F₂N₃O
• 分子量: 223.182
• InChiKey: KKAFLHVCHRPTSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-amino-1-(2,5-difluorophenyl)-1H-pyrazole-4-carbaldehyde 、 丙二酸二乙酯 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 ethyl 1-(2,5-difluorophenyl)-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carboxylate
  参考文献：
  名称：

  Discovery and Evaluation of 7-Alkyl-1,5-bis-aryl-pyrazolopyridinones as Highly Potent, Selective, and Orally Efficacious Inhibitors of p38α Mitogen-Activated Protein Kinase^⊥⊥ Atomic coordinates and structure factors for crystal structure of compound3dwith p38α can be accessed using PDB code 3LHJ.

  摘要：

  The p38 alpha mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1 beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38 alpha inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED50 <= 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.

  DOI：

  10.1021/jm100095x
• 作为产物：
  描述：

  在 水 作用下， 生成 5-amino-1-(2,5-difluorophenyl)-1H-pyrazole-4-carbaldehyde
  参考文献：
  名称：

  Discovery and Evaluation of 7-Alkyl-1,5-bis-aryl-pyrazolopyridinones as Highly Potent, Selective, and Orally Efficacious Inhibitors of p38α Mitogen-Activated Protein Kinase^⊥⊥ Atomic coordinates and structure factors for crystal structure of compound3dwith p38α can be accessed using PDB code 3LHJ.

  摘要：

  The p38 alpha mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1 beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38 alpha inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED50 <= 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.

  DOI：

  10.1021/jm100095x

文献信息

• Discovery and Evaluation of 7-Alkyl-1,5-bis-aryl-pyrazolopyridinones as Highly Potent, Selective, and Orally Efficacious Inhibitors of p38α Mitogen-Activated Protein Kinase^⊥⊥ Atomic coordinates and structure factors for crystal structure of compound<b>3d</b>with p38α can be accessed using PDB code 3LHJ.
  作者：Liping H. Pettus、Ryan P. Wurz、Shimin Xu、Brad Herberich、Bradley Henkle、Qiurong Liu、Helen J. McBride、Sharon Mu、Matthew H. Plant、Christiaan J. M. Saris、Lisa Sherman、Lu Min Wong、Samer Chmait、Matthew R. Lee、Christopher Mohr、Faye Hsieh、Andrew S. Tasker

  DOI：10.1021/jm100095x

  日期：2010.4.8

  The p38 alpha mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1 beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38 alpha inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED50 <= 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.