N-benzyl-1-(2-chloro-2-phenylethyl)-6-[(2-morpholin-4-ylethyl)thio]-1H-pyrazolo[3,4-d]pyrimidin-4-amine | 933770-90-2

• 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: N-benzyl-1-(2-chloro-2-phenylethyl)-6-[(2-morpholin-4-ylethyl)thio]-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• 英文别名: N-Benzyl-1-(2-chloro-2-phenylethyl)-6-[(2-morpholin-4-ylethyl)-thio]-1H-pyrazolo[3,4-d]pyrimidin-4-amine；N-benzyl-1-(2-chloro-2-phenylethyl)-6-(2-morpholin-4-ylethylsulfanyl)pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 933770-90-2
• 化学式: C₂₆H₂₉ClN₆OS
• 分子量: 509.075
• InChiKey: NBRVSSMSYRPVCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(2-氯乙基)吗啉 在 N,N-二甲基甲酰胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 38.0h， 生成 N-benzyl-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

文献信息

• COMPOUNDS AND USES THEREOF
  申请人：LEAD DISCOVERY SIENA S.R.L.

  公开号：US20180186796A1

  公开（公告）日：2018-07-05

  The present invention refers to 4-amino-substituted pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine derivatives of formula I and IV able to target the Src family kinases (SFKs) such as Src, Fyn and Hck tyrosine kinases as well as Abl tyrosine kinase and uses and method of preparation thereof. In particular, the compounds of the invention are for use in the treatment and/or prevention of cancer, such as neuroblastoma (NB) or glioblastoma multiforme (GBM) or for use in the treatment and/or prevention of neurodegenerative diseases such as taupathies.
• Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-<i>d</i>]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study
  作者：Marco Radi、Elena Dreassi、Chiara Brullo、Emmanuele Crespan、Cristina Tintori、Vincenzo Bernardo、Massimo Valoti、Claudio Zamperini、Henry Daigl、Francesca Musumeci、Fabio Carraro、Antonella Naldini、Irene Filippi、Giovanni Maga、Silvia Schenone、Maurizio Botta

  DOI：10.1021/jm1012819

  日期：2011.4.28

  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.