4-[4-[(R)-[2-(4-chlorophenyl)phenyl]sulfinyl]piperidin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide | 1616557-73-3

• 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-[4-[(R)-[2-(4-chlorophenyl)phenyl]sulfinyl]piperidin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide
• CAS: 1616557-73-3
• 化学式: C₄₅H₄₆ClF₃N₄O₇S₄
• 分子量: 975.595
• InChiKey: HLFFHNOYYAYEOQ-MQCLMNOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  64
• 可旋转键数：
  16
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  204
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  4-溴-N-Boc-哌啶 在 盐酸 、 4-二甲氨基吡啶 、 sodium periodate 、 四(三苯基膦)钯 、 水 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[4-[(R)-[2-(4-chlorophenyl)phenyl]sulfinyl]piperidin-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

文献信息

• Towards the next generation of dual Bcl-2/Bcl-xL inhibitors
  作者：Jeffrey G. Varnes、Thomas Gero、Shan Huang、R. Bruce Diebold、Claude Ogoe、Paul T. Grover、Mei Su、Prasenjit Mukherjee、Jamal Carlos Saeh、Terry MacIntyre、Galina Repik、Keith Dillman、Kate Byth、Daniel John Russell、Stephanos Ioannidis

  DOI：10.1016/j.bmcl.2014.05.036

  日期：2014.7

  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.