4-(1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-4-oxido-1,4-azaphosphinan-4-yl)benzoic acid | 1616557-94-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-4-oxido-1,4-azaphosphinan-4-yl)benzoic acid
• CAS: 1616557-94-8
• 化学式: C₂₄H₂₃ClNO₃P
• 分子量: 439.878
• InChiKey: JBONBTAUAGZRQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.21
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  57.61
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-[[(1R)-3-(4-吗啉)-1-[(苯基硫代)甲基]丙基]氨基]-3-[(三氟甲基)磺酰基]苯磺酰胺 、 4-(1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-4-oxido-1,4-azaphosphinan-4-yl)benzoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-[1-[[2-(4-chlorophenyl)phenyl]methyl]-4-oxo-1,4lambda5-azaphosphinan-4-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：

  methyl 4-(1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-4-oxido-1,4-azaphosphinan-4-yl)benzoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以93%的产率得到4-(1-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)-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