4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamine | 1023277-34-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamine
• 英文别名: 4-(3,3-Difluoro-1-methylpiperidin-4-yl)aniline
• CAS: 1023277-34-0
• 化学式: C₁₂H₁₆F₂N₂
• 分子量: 226.269
• InChiKey: BVUNWMURERGXIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-indan-5-yl-2-methylsulfonyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid methoxyamide 、 4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamine 在 溶剂黄146 作用下， 以58%的产率得到2-[4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamino]-8-indan-5-yl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid methoxyamide
  参考文献：
  名称：

  Pyrido[2,3-d]pyrimidin-5-ones: A Novel Class of Antiinflammatory Macrophage Colony-Stimulating Factor-1 Receptor Inhibitors

  摘要：

  A series of pyrido[2,3-d]pyrimidin-5-ones has been synthesized and evaluated as inhibitors of the kinase domain of macrophage colony-stimulating factor-1 receptor (FMS). FMS inhibitors may be useful in treating rheumatoid arthritis and other chronic inflammatory diseases. Structure-based optimization of the lead amide analogue 10 led to hydroxamate analogue 37, which possessed excellent potency and an improved pharmacokinetic profile. During the chronic phase of streptococcal cell wall-induced arthritis in rats, compound 37 (10, 3, and 1 mg/kg) was highly effective at reversing established joint swelling. In an adjuvant-induced arthritis model in rats, 37 prevented joint swelling partially at 10 mg/kg. In this model, osteoclastogenesis and bone erosion were prevented by low doses (1 or 0.33 mg/kg) that had minimal impact on inflammation. These data underscore the potential of FMS inhibitors to prevent erosions and reduce symptoms in rheumatoid arthritis.

  DOI：

  10.1021/jm801406h
• 作为产物：
  描述：

  [4-(3,3-difluoro-1-methylpiperidin-4-yl)phenyl]carbamic acid benzyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以80%的产率得到4-(3,3-difluoro-1-methylpiperidin-4-yl)phenylamine
  参考文献：
  名称：

  Pyrido[2,3-d]pyrimidin-5-ones: A Novel Class of Antiinflammatory Macrophage Colony-Stimulating Factor-1 Receptor Inhibitors

  摘要：

  A series of pyrido[2,3-d]pyrimidin-5-ones has been synthesized and evaluated as inhibitors of the kinase domain of macrophage colony-stimulating factor-1 receptor (FMS). FMS inhibitors may be useful in treating rheumatoid arthritis and other chronic inflammatory diseases. Structure-based optimization of the lead amide analogue 10 led to hydroxamate analogue 37, which possessed excellent potency and an improved pharmacokinetic profile. During the chronic phase of streptococcal cell wall-induced arthritis in rats, compound 37 (10, 3, and 1 mg/kg) was highly effective at reversing established joint swelling. In an adjuvant-induced arthritis model in rats, 37 prevented joint swelling partially at 10 mg/kg. In this model, osteoclastogenesis and bone erosion were prevented by low doses (1 or 0.33 mg/kg) that had minimal impact on inflammation. These data underscore the potential of FMS inhibitors to prevent erosions and reduce symptoms in rheumatoid arthritis.

  DOI：

  10.1021/jm801406h

文献信息

• Pyrido[2,3-<i>d</i>]pyrimidin-5-ones: A Novel Class of Antiinflammatory Macrophage Colony-Stimulating Factor-1 Receptor Inhibitors
  作者：Hui Huang、Daniel A. Hutta、James M. Rinker、Huaping Hu、William H. Parsons、Carsten Schubert、Renee L. DesJarlais、Carl S. Crysler、Margery A. Chaikin、Robert R. Donatelli、Yanmin Chen、Deping Cheng、Zhao Zhou、Edward Yurkow、Carl L. Manthey、Mark R. Player

  DOI：10.1021/jm801406h

  日期：2009.2.26

  A series of pyrido[2,3-d]pyrimidin-5-ones has been synthesized and evaluated as inhibitors of the kinase domain of macrophage colony-stimulating factor-1 receptor (FMS). FMS inhibitors may be useful in treating rheumatoid arthritis and other chronic inflammatory diseases. Structure-based optimization of the lead amide analogue 10 led to hydroxamate analogue 37, which possessed excellent potency and an improved pharmacokinetic profile. During the chronic phase of streptococcal cell wall-induced arthritis in rats, compound 37 (10, 3, and 1 mg/kg) was highly effective at reversing established joint swelling. In an adjuvant-induced arthritis model in rats, 37 prevented joint swelling partially at 10 mg/kg. In this model, osteoclastogenesis and bone erosion were prevented by low doses (1 or 0.33 mg/kg) that had minimal impact on inflammation. These data underscore the potential of FMS inhibitors to prevent erosions and reduce symptoms in rheumatoid arthritis.