5-amino-1-(2,4-difluorophenyl)-1H-pyrazole-4-carbaldehyde | 1220512-63-9

• 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-(2,4-difluorophenyl)-1H-pyrazole-4-carbaldehyde
• 英文别名: 5-amino-1-(2,4-difluorophenyl)pyrazole-4-carbaldehyde
• CAS: 1220512-63-9
• 化学式: C₁₀H₇F₂N₃O
• 分子量: 223.182
• InChiKey: NQBMPHHUMPFSEU-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-(2,4-difluorophenyl)-1H-pyrazole-4-carbaldehyde 在 哌啶 、 N-溴代丁二酰亚胺(NBS) 、 lithium acetate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 48.0h， 生成 5-bromo-1-(2,4-difluorophenyl)-1H-pyrazolo[3,4-b]pyridin-6(7H)-one
  参考文献：
  名称：

  Development of a Practical Synthesis of a Pyrazolopyridinone-Based p38 MAP Kinase Inhibitor

  摘要：

  A practical synthesis of the pyrazolopyridinone-based p38 MAP kinase inhibitor (4) was required for an ongoing program. The synthesis of a key pyrazolopyridinone building block was refined and optimized to provide kilogram quantities of 10 without chromatography or extractive workups. An efficient building-block strategy was employed to give optimal control of the key quality attributes, and in situ Raman spectroscopy was used to monitor and understand the complex solid-state properties of 4.

  DOI：

  10.1021/op100205s
• 作为产物：
  描述：

  在 水 作用下， 生成 5-amino-1-(2,4-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

• Pyridin-2-one Synthesis Using Ester Enolates and Aryl Aminoaldehydes and Ketones
  作者：Tushar Apsunde、Ryan P. Wurz

  DOI：10.1021/jo500284n

  日期：2014.4.4

  An aldol-like cyclocondensation has been used to prepare heterocyclic-fused pyridin-2-ones from aminoaldehydes and ketones upon treatment with a lithium enolate of ethyl acetate or alpha-substituted acetates. These motifs are present in a large number of biologically active natural products and synthetic compounds and can be accessed using mild reaction conditions using readily available starting materials. This methodology allows access to pyrimidinopyridin-2-ones, pyrazolopyridin-2-ones, and pyridopyridazine diones with varying substitution patterns.