3-(1-cyclopentylpyrazol-4-yl)-N-(1-methylpiperidin-4-yl)imidazo[1,2-b]pyridazin-6-amine | 1469884-05-6

• 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-(1-cyclopentylpyrazol-4-yl)-N-(1-methylpiperidin-4-yl)imidazo[1,2-b]pyridazin-6-amine
• CAS: 1469884-05-6
• 化学式: C₂₀H₂₇N₇
• 分子量: 365.481
• InChiKey: QHDIANPQDMRPCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-环戊基-1H-吡唑-4-硼酸频那醇酯 、 3-bromo-N-(1-methylpiperidin-4-yl)imidazo[1,2-b]pyridazin-6-amine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-(1-cyclopentylpyrazol-4-yl)-N-(1-methylpiperidin-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

文献信息

• Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole linked analogues
  作者：Jonathan M. Large、Simon A. Osborne、Ela Smiljanic-Hurley、Keith H. Ansell、Hayley M. Jones、Debra L. Taylor、Barbara Clough、Judith L. Green、Anthony A. Holder

  DOI：10.1016/j.bmcl.2013.08.010

  日期：2013.11

  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.