4-(1-(tert-Butoxycarbonyl)-4-oxido-1,4-azaphosphinan-4-yl)benzoic acid | 1616558-17-8

• 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: 4-(1-(tert-Butoxycarbonyl)-4-oxido-1,4-azaphosphinan-4-yl)benzoic acid
• 英文别名: 4-[1-[(2-methylpropan-2-yl)oxycarbonyl]-4-oxo-1,4λ5-azaphosphinan-4-yl]benzoic acid
• CAS: 1616558-17-8
• 化学式: C₁₆H₂₂NO₅P
• 分子量: 339.328
• InChiKey: RGRWANINAJMBRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  83.91
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(1-(tert-Butoxycarbonyl)-4-oxido-1,4-azaphosphinan-4-yl)benzoic acid 在 盐酸 、 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 methyl 4-(1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-4-oxido-1,4-azaphosphinan-4-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
• 作为产物：
  描述：

  tert-Butyl 4-(4-formylphenyl)-1,4-azaphosphinane-1-carboxylate 4-oxide 在 potassium permanganate 作用下， 以 丙酮 为溶剂， 以80%的产率得到4-(1-(tert-Butoxycarbonyl)-4-oxido-1,4-azaphosphinan-4-yl)benzoic acid
  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