3-bromo-6-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazine | 1033244-97-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-bromo-6-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazine
• 英文别名: tert-butyl N-(3-bromoimidazo[1,2-b]pyridazin-6-yl)-N-(cyclopropylmethyl)carbamate
• CAS: 1033244-97-1
• 化学式: C₁₅H₁₉BrN₄O₂
• 分子量: 367.245
• InChiKey: YITVFHKQILMSBM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  59.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3-bromo-6-[(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazine 、 二碳酸二叔丁酯 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以93%的产率得到3-bromo-6-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]imidazo[1,2-b]pyridazine
  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

文献信息

• Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 3: Exploration of effective compounds in arthritis models
  作者：Hiroki Shimizu、Tomonori Yamasaki、Yoshiyuki Yoneda、Fumihito Muro、Tomoaki Hamada、Takanori Yasukochi、Shinji Tanaka、Tadashi Toki、Mika Yokoyama、Kaoru Morishita、Shin Iimura

  DOI：10.1016/j.bmcl.2011.05.115

  日期：2011.8

  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.