2-(4-benzylamino-1-styryl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-ethanol | 1262793-58-7

• 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: 2-(4-benzylamino-1-styryl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-ethanol
• 英文别名: 2-[[4-(Benzylamino)-1-(2-phenylethenyl)pyrazolo[3,4-d]pyrimidin-6-yl]amino]ethanol
• CAS: 1262793-58-7
• 化学式: C₂₂H₂₂N₆O
• 分子量: 386.456
• InChiKey: DLPAKDXKUDZDMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  87.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(2-羟基-2-苯基乙基)-6-(甲硫基)-1,5-二氢-4H-吡唑并[3,4-d]嘧啶-4-酮 在 间氯过氧苯甲酸 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 氯仿 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 正丁醇 为溶剂， 反应 71.0h， 生成 2-(4-benzylamino-1-styryl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino)-ethanol
  参考文献：
  名称：

  Studies on the ATP Binding Site of Fyn Kinase for the Identification of New Inhibitors and Their Evaluation as Potential Agents against Tauopathies and Tumors

  摘要：

  Fyn is a member of the Src-family of nonreceptor protein-tyrosine kinases. Its abnormal activity has been shown to be related to various human cancers as well as to severe pathologies,; such as Alzheimer's and Parkinson's diseases. Herein, a structure-based drug design protocol was employed aimed at identifying novel Fyn inhibitors. Two hits from commercial sources (1, 2) were found active against Fyn with K-i of about 2 mu M, while derivative 4a, derived from our internal library, showed a K-i of 0.9 mu M. A hit-to-lead optimization effort was then initiated on derivative 4a to improve its potency. Slightly modifications rapidly determine an increase in the binding affinity, with the best inhibitors 4c and 44 having K(i)s of 70 and 95 nM, respectively. Both compounds were found able to inhibit the phosphorylation of : the protein Tau in an Alzheimer's model cell line and showed antiproliferative activities against different cancer cell lines.

  DOI：

  10.1021/acs.jmedchem.5b00140

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.