4-[6-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl]-2-fluorobenzoic acid | 1033245-04-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[6-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl]-2-fluorobenzoic acid
• 英文别名: 4-[6-[Cyclopropylmethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]imidazo[1,2-b]pyridazin-3-yl]-2-fluorobenzoic acid
• CAS: 1033245-04-3
• 化学式: C₂₂H₂₃FN₄O₄
• 分子量: 426.447
• InChiKey: PEIKMIXPYZFVMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[6-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl]-2-fluorobenzoic acid 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 4-[6-(cyclopropylmethylamino)imidazo[1,2-b]pyridazin-3-yl]-N-[2-(dimethylamino)ethyl]-2-fluorobenzamide
  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-羧基-3-氟苯硼酸 、 3-bromo-6-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazine 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以81%的产率得到4-[6-[(tert-butoxycarbonyl)(cyclopropylmethyl)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