4-chloro-1-[2-chloro-2-(4-methylphenyl)ethyl]-1H-pyrazolo[3,4-d]pyrimidine | 1443752-70-2

• 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: 4-chloro-1-[2-chloro-2-(4-methylphenyl)ethyl]-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 4-chloro-1-(2-chloro-2-(p-tolyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidine；4-Chloro-1-[2-chloro-2-(4-methylphenyl)ethyl]pyrazolo[3,4-d]pyrimidine；4-chloro-1-[2-chloro-2-(4-methylphenyl)ethyl]pyrazolo[3,4-d]pyrimidine
• CAS: 1443752-70-2
• 化学式: C₁₄H₁₂Cl₂N₄
• 分子量: 307.182
• InChiKey: XLKUZDQYRPARBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-1-[2-chloro-2-(4-methylphenyl)ethyl]-1H-pyrazolo[3,4-d]pyrimidine 、 苯胺 在 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 以60%的产率得到1-[2-chloro-2-(4-methylphenyl)ethyl]-N-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  合成生物学上相关的1,4-二取代的吡唑并[3,4- d ]嘧啶的另一种合成方法

  摘要：

  已经开发了一种通用的合成1，4-二取代的吡唑并[3，4- d ]嘧啶的方法。从商业上可获得的别嘌呤醇开始，TBAF介导的N1官能化和随后的C4亲核取代，在微波辅助或标准加热条件下，可得到具有潜在生物学意义的高度官能化的吡唑并[3,4- d ]嘧啶。

  DOI：

  10.1016/j.tetlet.2013.07.069
• 作为产物：
  描述：

  别嘌醇 在 sodium tetrahydroborate 、 四丁基氟化铵 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 41.0h， 生成 4-chloro-1-[2-chloro-2-(4-methylphenyl)ethyl]-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Pyrazolo[3,4-d]pyrimidines Active in Vivo on the Bcr-Abl T315I Mutant

  摘要：

  Starting from our in-house library of pyrazolo, [3,4-d]pyrimidines, a cross-docking simulation was conducted, on Bcr-Abl T315I mutant. Among the selected, compounds; (2a-e), the 4-bromo derivative 2b showed the best activity against the Bcr-Abl T315I mutant. Deeper computational studies highlighted the importance of the bromine atom in the para position of the NI side chain phenyl,ring for the interaction with the T315I mutant. A series of 4;bromo derivatives was thin synthesized and biologically evaluated.: Compound 2j showed a good balance of different ADME properties, high activity in cell-free assays, and a submicromolar potency against T315I Bcr-Abl expressing cells. In addition, it was converted into a water-soluble formulation by liposome encapsulation, preserving a good activity on leukemic T315I cells and avoiding the use of DMSO as solubilizing agent. In vivo studies on mice inoculated with 32D-T315I cells and treated with 2j showed a more than 50% reduction in tumor volumes.

  DOI：

  10.1021/jm400233w

文献信息

• Design, Synthesis, and Biological Evaluation of Pyrazolo[3,4-<i>d</i>]pyrimidines Active in Vivo on the Bcr-Abl T315I Mutant
  作者：Marco Radi、Cristina Tintori、Francesca Musumeci、Chiara Brullo、Claudio Zamperini、Elena Dreassi、Anna Lucia Fallacara、Giulia Vignaroli、Emmanuele Crespan、Samantha Zanoli、Ilaria Laurenzana、Irene Filippi、Giovanni Maga、Silvia Schenone、Adriano Angelucci、Maurizio Botta

  DOI：10.1021/jm400233w

  日期：2013.7.11

  Starting from our in-house library of pyrazolo, [3,4-d]pyrimidines, a cross-docking simulation was conducted, on Bcr-Abl T315I mutant. Among the selected, compounds; (2a-e), the 4-bromo derivative 2b showed the best activity against the Bcr-Abl T315I mutant. Deeper computational studies highlighted the importance of the bromine atom in the para position of the NI side chain phenyl,ring for the interaction with the T315I mutant. A series of 4;bromo derivatives was thin synthesized and biologically evaluated.: Compound 2j showed a good balance of different ADME properties, high activity in cell-free assays, and a submicromolar potency against T315I Bcr-Abl expressing cells. In addition, it was converted into a water-soluble formulation by liposome encapsulation, preserving a good activity on leukemic T315I cells and avoiding the use of DMSO as solubilizing agent. In vivo studies on mice inoculated with 32D-T315I cells and treated with 2j showed a more than 50% reduction in tumor volumes.
• An alternative synthetic approach for the synthesis of biologically relevant 1,4-disubstituted pyrazolo[3,4-d]pyrimidines
  作者：Marco Radi、Vincenzo Bernardo、Giulia Vignaroli、Annalaura Brai、Mariangela Biava、Silvia Schenone、Maurizio Botta

  DOI：10.1016/j.tetlet.2013.07.069

  日期：2013.9

  A versatile approach for the synthesis of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines has been developed. Starting from commercially available allopurinol, TBAF mediated N1-functionalization and subsequent C4 nucleophilic substitution, under microwave assisted- or standard heating conditions, granted access to highly functionalized pyrazolo[3,4-d]pyrimidines of potential biological interest.

  已经开发了一种通用的合成1，4-二取代的吡唑并[3，4- d ]嘧啶的方法。从商业上可获得的别嘌呤醇开始，TBAF介导的N1官能化和随后的C4亲核取代，在微波辅助或标准加热条件下，可得到具有潜在生物学意义的高度官能化的吡唑并[3,4- d ]嘧啶。