4-chloro-3-{[6-(methylthio)-1-(2-phenylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino}phenol

• 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: 4-chloro-3-{[6-(methylthio)-1-(2-phenylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino}phenol
• 英文别名: 4-Chloro-3-[[6-methylsulfanyl-1-(2-phenylpropyl)pyrazolo[3,4-d]pyrimidin-4-yl]amino]phenol；4-chloro-3-[[6-methylsulfanyl-1-(2-phenylpropyl)pyrazolo[3,4-d]pyrimidin-4-yl]amino]phenol
• 化学式: C₂₁H₂₀ClN₅OS
• 分子量: 425.942
• InChiKey: WMAZRAKOIJGGJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 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：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-chloro-3-{[6-(methylthio)-1-(2-phenylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino}phenol 、 C.I.酸性橙108 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 二甲基亚砜 、 正丁醇 为溶剂， 反应 9.0h， 以65%的产率得到4-chloro-3-{[6-[(2-hydroxyethyl)amino]-1-(2-phenylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino}phenol
  参考文献：
  名称：

  Efficient optimization of pyrazolo[3,4-d]pyrimidines derivatives as c-Src kinase inhibitors in neuroblastoma treatment

  摘要：

  The proto-oncogene c-Src is a non-receptor tyrosine kinase which is involved in the regulation of many cellular processes, such as differentiation, adhesion and survival. c-Src hyperactivation has been detected in many tumors, including neuroblastoma (NB), one of the major causes of death from neoplasia in infancy. We already reported a large family of pyrazolo[3,4-d]pyrimidines active as c-Src inhibitors. Interestingly, some of these derivatives resulted also active on SH-SY5Y NB cell line. Herein, starting from our previous Free Energy Perturbation/Monte Carlo calculations, we report an optimization study which led to the identification of a new series of derivatives endowed with nanomolar K-i values against c-Src, interesting antiproliferative activity on SH-SY5Y cells and a suitable ADME profile.

  DOI：

  10.1016/j.bmcl.2018.09.024
• 作为产物：
  描述：

  4-氯-3-硝基苯酚 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 9.0h， 生成 4-chloro-3-{[6-(methylthio)-1-(2-phenylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]amino}phenol
  参考文献：
  名称：

  Efficient optimization of pyrazolo[3,4-d]pyrimidines derivatives as c-Src kinase inhibitors in neuroblastoma treatment

  摘要：

  The proto-oncogene c-Src is a non-receptor tyrosine kinase which is involved in the regulation of many cellular processes, such as differentiation, adhesion and survival. c-Src hyperactivation has been detected in many tumors, including neuroblastoma (NB), one of the major causes of death from neoplasia in infancy. We already reported a large family of pyrazolo[3,4-d]pyrimidines active as c-Src inhibitors. Interestingly, some of these derivatives resulted also active on SH-SY5Y NB cell line. Herein, starting from our previous Free Energy Perturbation/Monte Carlo calculations, we report an optimization study which led to the identification of a new series of derivatives endowed with nanomolar K-i values against c-Src, interesting antiproliferative activity on SH-SY5Y cells and a suitable ADME profile.

  DOI：

  10.1016/j.bmcl.2018.09.024

文献信息

• Novel pyrazolo[3,4-d]pyrimidines as dual Src/Bcr-Abl kinase inhibitors: Synthesis and biological evaluation for chronic myeloid leukemia treatment
  作者：Salvatore Di Maria、Francesca Picarazzi、Mattia Mori、Annarita Cianciusi、Anna Carbone、Emmanuele Crespan、Cecilia Perini、Samantha Sabetta、Serenella Deplano、Federica Poggialini、Alessio Molinari、Rossella Aronne、Elias Maccioni、Giovanni Maga、Adriano Angelucci、Silvia Schenone、Francesca Musumeci、Elena Dreassi

  DOI：10.1016/j.bioorg.2022.106071

  日期：2022.11

  molecules active as dual Src/Bcr-Abl inhibitors emerged as effective targeted therapies for CML and a few compounds are currently in clinical use. In this study, we applied a target-oriented approach to identify a family of pyrazolo[3,4-d]pyrimidines as dual Src/Bcr-Abl inhibitors as anti-leukemia agents. Considering the high homology between Src and Bcr-Abl, in-house Src inhibitors 8a-l and new analogue compounds

  Bcr-Abl 酪氨酸激酶 (TK) 是慢性粒细胞白血病 (CML) 的分子标志。Src 是另一种 TK 激酶，其参与 CML 已被广泛证实。作为双 Src/Bcr-Abl 抑制剂活性的小分子作为 CML 的有效靶向疗法出现，一些化合物目前正在临床使用。在这项研究中，我们应用了一种靶向方法来确定吡唑并[3,4- d ]嘧啶家族作为双 Src/Bcr-Abl 抑制剂作为抗白血病药物。考虑到 Src 和 Bcr-Abl 之间的高度同源性，内部Src 抑制剂8a-l和新的类似化合物9a-n被筛选为双重 Src/Bcr-Abl 抑制剂。确定了最有希望的化合物对 K562 CML 细胞的抗增殖活性和 ADME 谱。分子模型研究阐明了抑制剂与 Bcr-Abl (wt) 催化口袋的结合模式。化合物8j和8k在酶促和细胞测定中显示出纳摩尔活性，以及​​良好的 ADME 特性，成为 CML 治疗的有希望的候