1-(2-hydroxy-2-phenylethyl)-6-[(2-morpholin-4-ylethyl)thio]-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one | 1283727-42-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 1-(2-hydroxy-2-phenylethyl)-6-[(2-morpholin-4-ylethyl)thio]-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one
• 英文别名: 1-(2-hydroxy-2-phenylethyl)-6-(2-morpholin-4-ylethylsulfanyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one
• CAS: 1283727-42-3
• 化学式: C₁₉H₂₃N₅O₃S
• 分子量: 401.489
• InChiKey: JGZKTHVWDWYXPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-hydroxy-2-phenylethyl)-6-[(2-morpholin-4-ylethyl)thio]-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 在 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 8.0h， 生成 N-(3-chlorophenyl)-1-(2-chloro-2-phenylethyl)-6-[(2-morpholin-4-ylethyl)thio]-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-d]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study

  摘要：

  A family of dual Src/Abl inhibitors characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold was previously reported by us and proved to be active against several tumor cell lines. Among these compounds, a promising antileukemia lead (1) has been recently identified, but, unfortunately, it suffers from substandard pharmaceutical properties. Accordingly, an approach for the optimization of the lead 1 is described in the present work. A series of more soluble pyrazolo[3,4-d]pyrimidine derivatives were rationally designed and proved to maintain the dual Src/Abl activity of the lead. Selected compounds showed an interesting activity profile against three different leukemic cells also in hypoxic conditions, which are usually characterized by imatinib-resistance. Finally, in vitro ADME properties (PAMPA permeation, water solubility, microsomal stability) for the most promising inhibitors were also evaluated, thus allowing the identification of a few optimized analogues of lead 1 as promising antileukemia agents.

  DOI：

  10.1021/jm1012819
• 作为产物：
  描述：

  4-(2-氯乙基)吗啉 、 1-(2-hydroxy-2-phenylethyl)-6-thioxo-1,5,6,7-tetrahydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 在 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以63%的产率得到1-(2-hydroxy-2-phenylethyl)-6-[(2-morpholin-4-ylethyl)thio]-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one
  参考文献：
  名称：

  Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-d]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study

  摘要：

  A family of dual Src/Abl inhibitors characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold was previously reported by us and proved to be active against several tumor cell lines. Among these compounds, a promising antileukemia lead (1) has been recently identified, but, unfortunately, it suffers from substandard pharmaceutical properties. Accordingly, an approach for the optimization of the lead 1 is described in the present work. A series of more soluble pyrazolo[3,4-d]pyrimidine derivatives were rationally designed and proved to maintain the dual Src/Abl activity of the lead. Selected compounds showed an interesting activity profile against three different leukemic cells also in hypoxic conditions, which are usually characterized by imatinib-resistance. Finally, in vitro ADME properties (PAMPA permeation, water solubility, microsomal stability) for the most promising inhibitors were also evaluated, thus allowing the identification of a few optimized analogues of lead 1 as promising antileukemia agents.

  DOI：

  10.1021/jm1012819