1-(2-methoxy-2-phenylethyl)-6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine | 1583284-94-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-methoxy-2-phenylethyl)-6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• 英文别名: 1-(2-Methoxy-2-phenylethyl)-6-methylsulfanyl-3-phenylpyrazolo[3,4-d]pyrimidin-4-amine；1-(2-methoxy-2-phenylethyl)-6-methylsulfanyl-3-phenylpyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 1583284-94-9
• 化学式: C₂₁H₂₁N₅OS
• 分子量: 391.497
• InChiKey: DGZMKJMPNOAZTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2-methoxy-2-phenylethyl)-6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine 在 10 wt% Pd(OH)2 on carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以87%的产率得到1-(2-methoxy-2-phenylethyl)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  探索特权吡唑并[3,4- d ]嘧啶支架周围的化学空间：寻求新型的T315I突变型Abl的变构抑制剂

  摘要：

  具有高水平分子多样性的吡唑并[3,4- d ]嘧啶文库已通过应用允许C3，N1，C4和C6取代的合成序列开发而成。对这种基于“特权支架”的化合物集合的酶促筛选，证实了在以目标为导向的合成为特征的领域中，以多样性为导向的方法的使用。实际上，几种化合物对选定的激酶表现出高活性（即Src，Abl wt和T315I突变形式），而且有趣的是，新化合物作为A315的T315I突变形式的变构抑制剂出现了，打开了大门。开发新型非竞争性Abl抑制剂（T315I）的新机会。

  DOI：

  10.1021/co500004e
• 作为产物：
  描述：

  4-chloro-1-(2-methoxy-2-phenylethyl)-6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidine 在 氨 作用下， 以 甲醇 、 乙醇 为溶剂， 以92%的产率得到1-(2-methoxy-2-phenylethyl)-6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  探索特权吡唑并[3,4- d ]嘧啶支架周围的化学空间：寻求新型的T315I突变型Abl的变构抑制剂

  摘要：

  具有高水平分子多样性的吡唑并[3,4- d ]嘧啶文库已通过应用允许C3，N1，C4和C6取代的合成序列开发而成。对这种基于“特权支架”的化合物集合的酶促筛选，证实了在以目标为导向的合成为特征的领域中，以多样性为导向的方法的使用。实际上，几种化合物对选定的激酶表现出高活性（即Src，Abl wt和T315I突变形式），而且有趣的是，新化合物作为A315的T315I突变形式的变构抑制剂出现了，打开了大门。开发新型非竞争性Abl抑制剂（T315I）的新机会。

  DOI：

  10.1021/co500004e

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.
• [EN] COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS
  申请人：LEAD DISCOVERY SIENA S R L

  公开号：WO2016066755A2

  公开（公告）日：2016-05-06

  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.
• Exploring the Chemical Space around the Privileged Pyrazolo[3,4-<i>d</i>]pyrimidine Scaffold: Toward Novel Allosteric Inhibitors of T315I-Mutated Abl
  作者：Giulia Vignaroli、Martina Mencarelli、Deborah Sementa、Emmanuele Crespan、Miroslava Kissova、Giovanni Maga、Silvia Schenone、Marco Radi、Maurizio Botta

  DOI：10.1021/co500004e

  日期：2014.4.14

  screening of this “privileged scaffold”-based compound collection, validated the use of a diversity-oriented approach in a field characteristically explored by target-oriented synthesis. In fact, several compounds showed high activity against the selected kinases (i.e., Src, Abl wt, and T315I mutated-form), furthermore and interestingly a new compound has emerged as an allosteric inhibitor of the T315I mutated-form

  具有高水平分子多样性的吡唑并[3,4- d ]嘧啶文库已通过应用允许C3，N1，C4和C6取代的合成序列开发而成。对这种基于“特权支架”的化合物集合的酶促筛选，证实了在以目标为导向的合成为特征的领域中，以多样性为导向的方法的使用。实际上，几种化合物对选定的激酶表现出高活性（即Src，Abl wt和T315I突变形式），而且有趣的是，新化合物作为A315的T315I突变形式的变构抑制剂出现了，打开了大门。开发新型非竞争性Abl抑制剂（T315I）的新机会。
• 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
  作者：Cristina Tintori、Giuseppina La Sala、Giulia Vignaroli、Lorenzo Botta、Anna Lucia Fallacara、Federico Falchi、Marco Radi、Claudio Zamperini、Elena Dreassi、Lucia Dello Iacono、Donata Orioli、Giuseppe Biamonti、Mirko Garbelli、Andrea Lossani、Francesca Gasparrini、Tiziano Tuccinardi、Ilaria Laurenzana、Adriano Angelucci、Giovanni Maga、Silvia Schenone、Chiara Brullo、Francesca Musumeci、Andrea Desogus、Emmanuele Crespan、Maurizio Botta

  DOI：10.1021/acs.jmedchem.5b00140

  日期：2015.6.11

  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.