4-[6-[[(1,1-Dimethylethoxy)carbonyl](4-fluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl]-2-fluorobenzoic acid | 1138324-49-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[6-[[(1,1-Dimethylethoxy)carbonyl](4-fluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl]-2-fluorobenzoic acid
• 英文别名: 2-fluoro-4-[6-[4-fluorobutyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]imidazo[1,2-b]pyridazin-3-yl]benzoic acid
• CAS: 1138324-49-8
• 化学式: C₂₂H₂₄F₂N₄O₄
• 分子量: 446.454
• InChiKey: SJVYJWUBXYCIAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.72
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.03
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2S,4R)-2-(氨基甲基)-4-氟吡咯烷-1-羧酸叔丁酯 、 4-[6-[[(1,1-Dimethylethoxy)carbonyl](4-fluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl]-2-fluorobenzoic acid 在 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以100%的产率得到tert-butyl (2S,4R)-2-((4-(6-((tert-butoxycarbonyl)(4-fluorobutyl)amino)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzamido)methyl)-4-fluoropyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 3: Exploration of effective compounds in arthritis models

  摘要：

  We have discovered imidazo[1,2-b]pyridazine derivatives that show suppressive activity of inflammation in arthritis models. We optimized the substructures of imidazo[1,2-b] pyridazine derivatives to combine potent IKK beta inhibitory activity, TNF alpha inhibitory activity in vivo and excellent pharmacokinetics. The compound we have acquired, which had both potent activities and good pharmacokinetic profiles based on improved physicochemical properties, demonstrated efficacy on collagen-induced arthritis models in mice and rats. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.115
• 作为产物：
  描述：

  4-((3-bromoimidazo[1,2-b]pyridazin-6-yl)(4-methoxybenzyl)amino)butyl methanesulfonate 在 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 四丁基氟化铵 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 生成 4-[6-[[(1,1-Dimethylethoxy)carbonyl](4-fluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl]-2-fluorobenzoic acid
  参考文献：
  名称：

  Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 3: Exploration of effective compounds in arthritis models

  摘要：

  We have discovered imidazo[1,2-b]pyridazine derivatives that show suppressive activity of inflammation in arthritis models. We optimized the substructures of imidazo[1,2-b] pyridazine derivatives to combine potent IKK beta inhibitory activity, TNF alpha inhibitory activity in vivo and excellent pharmacokinetics. The compound we have acquired, which had both potent activities and good pharmacokinetic profiles based on improved physicochemical properties, demonstrated efficacy on collagen-induced arthritis models in mice and rats. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.115