N-[3,5-bis(trifluoromethyl)benzyl]-1-[2-(4-bromophenyl)-2-chloroethyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine | 1443752-65-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3,5-bis(trifluoromethyl)benzyl]-1-[2-(4-bromophenyl)-2-chloroethyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• 英文别名: N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-1-[2-(4-bromophenyl)-2-chloroethyl]pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 1443752-65-5
• 化学式: C₂₂H₁₅BrClF₆N₅
• 分子量: 578.742
• InChiKey: CMBWCUKJTFCGST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-(2-(4-bromophenyl)-2-chloroethyl)-4-chloro-1H-pyrazolo[3,4-d]pyrimidine 、 3,5-双(三氟甲基)苄胺 以 甲苯 为溶剂， 以56%的产率得到N-[3,5-bis(trifluoromethyl)benzyl]-1-[2-(4-bromophenyl)-2-chloroethyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  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.