tert-butyl 4-((3-(1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl)amino)piperidine-1-carboxylate | 1469884-32-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-((3-(1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl)amino)piperidine-1-carboxylate
• CAS: 1469884-32-9
• 化学式: C₁₉H₂₅N₇O₂
• 分子量: 383.453
• InChiKey: SNIDECFBKSZPII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  100.44
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((3-(1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl)amino)piperidine-1-carboxylate 在 盐酸 、 copper(l) iodide 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 L-脯氨酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二甲基亚砜 为溶剂， 生成 N-(1-methylpiperidin-4-yl)-3-[1-(pyrazin-2-yI)-1H-pyrazol-4-yl]imidazo[1,2-b]pyridazin-6-amine
  参考文献：
  名称：

  Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole linked analogues

  摘要：

  The structural diversity and SAR in a series of imidazopyridazine inhibitors of Plasmodium falciparum calcium dependent protein kinase 1 (PfCDPK1) has been explored and extended. The opportunity to further improve key ADME parameters by means of lowering log D was identified, and this was achieved by replacement of a six-membered (hetero)aromatic linker with a pyrazole. A short SAR study has delivered key examples with useful in vitro activity and ADME profiles, good selectivity against a human kinase panel and improved levels of lipophilic ligand efficiency. These new analogues thus provide a credible additional route to further development of the series. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.010
• 作为产物：
  描述：

  1-Boc-吡唑-4-硼酸频哪醇酯 、 tert-butyl 4-[(3-bromoimidazo[1,2-b]pyridazin-6-yl)amino]piperidine-1-carboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 tert-butyl 4-((3-(1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl)amino)piperidine-1-carboxylate
  参考文献：
  名称：

  Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole linked analogues

  摘要：

  The structural diversity and SAR in a series of imidazopyridazine inhibitors of Plasmodium falciparum calcium dependent protein kinase 1 (PfCDPK1) has been explored and extended. The opportunity to further improve key ADME parameters by means of lowering log D was identified, and this was achieved by replacement of a six-membered (hetero)aromatic linker with a pyrazole. A short SAR study has delivered key examples with useful in vitro activity and ADME profiles, good selectivity against a human kinase panel and improved levels of lipophilic ligand efficiency. These new analogues thus provide a credible additional route to further development of the series. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.010