ethyl 4-(4-(2-bromo-6-hydroxybenzyl)piperazin-1-yl)benzoate | 1616558-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ethyl 4-(4-(2-bromo-6-hydroxybenzyl)piperazin-1-yl)benzoate
• CAS: 1616558-06-5
• 化学式: C₂₀H₂₃BrN₂O₃
• 分子量: 419.318
• InChiKey: JNMJFCXYVRHYTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.65
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  53.01
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-(2-bromo-6-hydroxybenzyl)piperazin-1-yl)benzoate 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 hydridocarbonylbis(triphenylphosphine)rhodium(I) 、 二苯基硅烷 、 水 、 sodium hydride 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[4-[[2-(4-chlorophenyl)-6-[2-(dimethylamino)ethoxy]phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide
  参考文献：
  名称：

  Towards the next generation of dual Bcl-2/Bcl-xL inhibitors

  摘要：

  Structural modifications of the left-hand side of compound 1 were identified which retained or improved potent binding to Bcl-2 and Bcl-x(L) in in vitro biochemical assays and had strong activity in an RS4;11 apoptotic cellular assay. For example, sulfoxide diastereomer 13 maintained good binding affinity and comparable cellular potency to 1 while improving aqueous solubility. The corresponding diastereomer (14) was significantly less potent in the cell, and docking studies suggest that this is due to a stereochemical preference for the R-S versus S-S sulfoxide. Appending a dimethylaminoethoxy side chain (27) adjacent to the benzylic position of the biphenyl moiety of 1 improved cellular activity by approximately threefold, and this activity was corroborated in cell lines overexpressing Bcl-2 and Bcl-x(L). (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.036
• 作为产物：
  描述：

  4-(1-哌嗪基)苯甲酸乙酯 、 2-溴-6-羟基苯甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 以98%的产率得到ethyl 4-(4-(2-bromo-6-hydroxybenzyl)piperazin-1-yl)benzoate
  参考文献：
  名称：

  Towards the next generation of dual Bcl-2/Bcl-xL inhibitors

  摘要：

  Structural modifications of the left-hand side of compound 1 were identified which retained or improved potent binding to Bcl-2 and Bcl-x(L) in in vitro biochemical assays and had strong activity in an RS4;11 apoptotic cellular assay. For example, sulfoxide diastereomer 13 maintained good binding affinity and comparable cellular potency to 1 while improving aqueous solubility. The corresponding diastereomer (14) was significantly less potent in the cell, and docking studies suggest that this is due to a stereochemical preference for the R-S versus S-S sulfoxide. Appending a dimethylaminoethoxy side chain (27) adjacent to the benzylic position of the biphenyl moiety of 1 improved cellular activity by approximately threefold, and this activity was corroborated in cell lines overexpressing Bcl-2 and Bcl-x(L). (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.036