4-((4-(6-((cyclopropylmethyl)amino)imidazo[1,2-b]pyridazin-3-yl)-N-(((2S,4R)-4-fluoropyrrolidin-2-yl)methyl)benzamido)methyl)benzoic acid | 1272598-62-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((4-(6-((cyclopropylmethyl)amino)imidazo[1,2-b]pyridazin-3-yl)-N-(((2S,4R)-4-fluoropyrrolidin-2-yl)methyl)benzamido)methyl)benzoic acid
• CAS: 1272598-62-5
• 化学式: C₃₂H₄₁FN₆O₅
• 分子量: 608.713
• InChiKey: UJVGBORGXHHHLO-RPWUZVMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.63
• 重原子数：
  44.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  118.37
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  4-((4-(6-((cyclopropylmethyl)amino)imidazo[1,2-b]pyridazin-3-yl)-N-(((2S,4R)-4-fluoropyrrolidin-2-yl)methyl)benzamido)methyl)benzoic acid 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 2: Improvement of potency in vitro and in vivo

  摘要：

  We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKK beta inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKK beta by the introduction of additional substituents based on the hypothesis derived from an interaction model study. These improved compounds showed inhibitory activity of TNF alpha production in mice. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.078
• 作为产物：
  描述：

  3-bromo-6-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazine 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-((4-(6-((cyclopropylmethyl)amino)imidazo[1,2-b]pyridazin-3-yl)-N-(((2S,4R)-4-fluoropyrrolidin-2-yl)methyl)benzamido)methyl)benzoic acid
  参考文献：
  名称：

  Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 2: Improvement of potency in vitro and in vivo

  摘要：

  We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKK beta inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKK beta by the introduction of additional substituents based on the hypothesis derived from an interaction model study. These improved compounds showed inhibitory activity of TNF alpha production in mice. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.078