2-(4-fluorophenyl)-3-(2-methylsulfanylpyrimidin-4-yl)-5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazin-1-one | 702695-62-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-fluorophenyl)-3-(2-methylsulfanylpyrimidin-4-yl)-5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazin-1-one
• CAS: 702695-62-3
• 化学式: C₁₈H₁₇FN₄OS
• 分子量: 356.424
• InChiKey: LYSDGCUDPGOVOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  52.71
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)-3-(2-methylsulfanylpyrimidin-4-yl)-5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazin-1-one 在 Oxone 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 3.0h， 生成 2-(4-fluorophenyl)-1-[2-[[(2S)-3-hydroxy-3-methylbutan-2-yl]amino]pyrimidin-4-yl]-5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazin-3-one
  参考文献：
  名称：

  Development of Orally Bioavailable Bicyclic Pyrazolones as Inhibitors of Tumor Necrosis Factor-α Production

  摘要：

  2-Aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel bicyclic pyrazolope core, are described. Many showed low-nanomolar activity against lipopolysaccharide-induced TNF-alpha production in monocytic cells. Secondary screening data are presented for the pyrimidinyl bicyclic pyrazolones. Several of these analogues showed good oral bioavailability in rat and efficacy in the rat iodoacetate in vivo model.

  DOI：

  10.1021/jm049968m
• 作为产物：
  描述：

  2-(methylsulfanyl)pyrimidine-4-carbonyl chloride 在 sodium hydroxide 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-fluorophenyl)-3-(2-methylsulfanylpyrimidin-4-yl)-5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazin-1-one
  参考文献：
  名称：

  Development of Orally Bioavailable Bicyclic Pyrazolones as Inhibitors of Tumor Necrosis Factor-α Production

  摘要：

  2-Aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel bicyclic pyrazolope core, are described. Many showed low-nanomolar activity against lipopolysaccharide-induced TNF-alpha production in monocytic cells. Secondary screening data are presented for the pyrimidinyl bicyclic pyrazolones. Several of these analogues showed good oral bioavailability in rat and efficacy in the rat iodoacetate in vivo model.

  DOI：

  10.1021/jm049968m