(ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl) (2S,2'S)-bis(2-(4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropanoate) | 1009309-64-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl) (2S,2'S)-bis(2-(4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropanoate)
• CAS: 1009309-64-1
• 化学式: C₃₀H₃₂N₂O₈S₄
• 分子量: 676.857
• InChiKey: VZNAUZHWUYYJRA-ZEQRLZLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  44.0
• 可旋转键数：
  17.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  111.68
• 氢给体数：
  0.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl) (2S,2'S)-bis(2-(4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropanoate) 、 对溴苯甲醛 在 ammonium acetate 作用下， 以 甲苯 为溶剂， 反应 16.0h， 生成 2-[2-[2-[(2S)-2-[(5Z)-5-[(4-bromophenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoyl]oxyethoxy]ethoxy]ethyl (2S)-2-[(5Z)-5-[(4-bromophenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoate
  参考文献：
  名称：

  Development of dimeric modulators for anti-apoptotic Bcl-2 proteins

  摘要：

  Bcl-2 family proteins can be classified into two subfamilies-anti-apoptotic members and pro-apoptotic members. Mechanistically, these two subfamilies can antagonize each other through heterodimerization while homodimerization has been proposed for each subfamily to carry out their corresponding anti-apoptotic or pro-apoptotic functions. To date, many small-molecule antagonists against anti-apoptotic Bcl-2 proteins have been developed, which are monomeric modulators. In this study, a series of BH3I-1 based dimeric modulators were developed with structure-activity relationship explored. Dimeric modulators compared to the monomeric antagonists have enhanced binding activity against anti-apoptotic Bcl-2 proteins. In addition, the acidic functional group was demonstrated to be critical for the binding interaction of the small-molecule antagonists with anti-apoptotic Bcl-2 proteins. Finally, the representative dimeric modulator revealed enhanced activity in inducing cytochrome c release from mitochondria compared to its monomeric counterpart. Taken together, dimerization of monomeric modulators is one practical approach to enhance the bioactivity of Bcl-2 antagonists. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.088
• 作为产物：
  描述：

  (S)-2-(4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropanoic acid 、 三乙二醇 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 12.0h， 生成 (ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl) (2S,2'S)-bis(2-(4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropanoate)
  参考文献：
  名称：

  Development of dimeric modulators for anti-apoptotic Bcl-2 proteins

  摘要：

  Bcl-2 family proteins can be classified into two subfamilies-anti-apoptotic members and pro-apoptotic members. Mechanistically, these two subfamilies can antagonize each other through heterodimerization while homodimerization has been proposed for each subfamily to carry out their corresponding anti-apoptotic or pro-apoptotic functions. To date, many small-molecule antagonists against anti-apoptotic Bcl-2 proteins have been developed, which are monomeric modulators. In this study, a series of BH3I-1 based dimeric modulators were developed with structure-activity relationship explored. Dimeric modulators compared to the monomeric antagonists have enhanced binding activity against anti-apoptotic Bcl-2 proteins. In addition, the acidic functional group was demonstrated to be critical for the binding interaction of the small-molecule antagonists with anti-apoptotic Bcl-2 proteins. Finally, the representative dimeric modulator revealed enhanced activity in inducing cytochrome c release from mitochondria compared to its monomeric counterpart. Taken together, dimerization of monomeric modulators is one practical approach to enhance the bioactivity of Bcl-2 antagonists. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.088