8-(pyridazin-4-yl)-1,4-dioxaspiro[4.5]decan-8-ol | 1289637-97-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-(pyridazin-4-yl)-1,4-dioxaspiro[4.5]decan-8-ol
• CAS: 1289637-97-3
• 化学式: C₁₂H₁₆N₂O₃
• 分子量: 236.271
• InChiKey: FJZPVYJCDRXAOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.98
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  64.47
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  8-(pyridazin-4-yl)-1,4-dioxaspiro[4.5]decan-8-ol 在 盐酸 、 水 作用下， 以 四氢呋喃 为溶剂， 以50%的产率得到4-hydroxy-4-(pyridazin-4-yl)cyclohexanone
  参考文献：
  名称：

  Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist

  摘要：

  We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 mu M in inhibition of the hERG potassium current, a free fraction of 58% in protein binding, high selectivity over other chemokine receptors and G-protein-coupled receptors, and acceptable oral bioavailability in rodents and primates. In human clinical trials, INCB3284 exhibited a pharmacokinetic profile suitable for once-a-day dosing (T-1/2 = 15 h).

  DOI：

  10.1021/ml200030q
• 作为产物：
  描述：

  哒嗪 、 1,4-环己二酮单乙二醇缩酮 在 2,2,6,6-tetramethylpiperidinyl-lithium 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 6.0h， 以12%的产率得到8-pyridazin-3-yl-1,4-dioxaspiro[4.5]decan-8-ol
  参考文献：
  名称：

  Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist

  摘要：

  We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 mu M in inhibition of the hERG potassium current, a free fraction of 58% in protein binding, high selectivity over other chemokine receptors and G-protein-coupled receptors, and acceptable oral bioavailability in rodents and primates. In human clinical trials, INCB3284 exhibited a pharmacokinetic profile suitable for once-a-day dosing (T-1/2 = 15 h).

  DOI：

  10.1021/ml200030q