4-[(E)-2-[[(E)-2-(3,4-dihydroxyphenyl)vinyl]sulfonylmethylsulfonyl]vinyl]benzene-1,2-diol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-[(E)-2-[[(E)-2-(3,4-dihydroxyphenyl)vinyl]sulfonylmethylsulfonyl]vinyl]benzene-1,2-diol
• 英文别名: 4-[(E)-2-[[(E)-2-(3,4-dihydroxyphenyl)ethenyl]sulfonylmethylsulfonyl]ethenyl]benzene-1,2-diol
• 化学式: C₁₇H₁₆O₈S₂
• 分子量: 412.441
• InChiKey: ZWYMHLMQJIRSFD-KQQUZDAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[(E)-2-[[(E)-2-(3,4-dihydroxyphenyl)vinyl]sulfonylmethylsulfonyl]vinyl]benzene-1,2-diol 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 96.0h， 以39%的产率得到bis(2-(3,4-dihydroxyphenyl)-ethylsulfonyl)methane
  参考文献：
  名称：

  环取代基对作为HIV-1抑制剂的乙烯基砜的生物活性的影响。

  摘要：

  在先前的研究中，我们准备了一个小型的菊苣酸类似物文库，该文库具有强大的抗整合酶和抗病毒活性。还显示出活性化合物分为两类之一：抑制病毒复制早期的化合物和抑制病毒复制的化合物。在这项研究中，已合成了一系列具有一系列环取代基的含乙烯基双膦二砜的化合物，以探讨结构对抑制机理的影响。使用HIV药物敏感性测定法鉴定了四种活性化合物。芳香环上没有取代基或没有吸电子取代基的三种抑制剂导致高水平的细胞毒性和抗病毒活性。迷恋电子效应对活动的潜在影响，我们研究了活性化合物是否可以通过1,4-加成发生非特异性反应。为了研究该假设，将化合物与谷胱甘肽一起孵育，并通过LC / MS分析，鉴定了与单加成和双加成加合物相对应的分子离子峰。其次，我们合成了缺乏参与1，4-加成能力的类似物，并测试了它们的抗病毒活性和细胞毒性，发现该化合物对这两种活性均无活性。综上所述，本文报道的研究表明，在芳环上缺乏供电子取代基的化合物是生

  DOI：

  10.1016/j.bmc.2006.10.017
• 作为产物：
  描述：

  bis(trans-β-3,4-diacetoxystyrenesulfonyl)methane 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.33h， 以100%的产率得到4-[(E)-2-[[(E)-2-(3,4-dihydroxyphenyl)vinyl]sulfonylmethylsulfonyl]vinyl]benzene-1,2-diol
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Geminal Disulfones as HIV-1 Integrase Inhibitors

  摘要：

  Integration of HIV-1 viral DNA into the host genome is carried out by HIV-integrase (IN) and is a critical step in viral replication. Although several classes of compounds have been reported to inhibit IN in enzymatic assays, inhibition is not always correlated with antiviral activity. Moreover, potent antiviral IN inhibitors such as the chicoric acids do not act upon the intended enzymatic target but behave as entry inhibitors instead. The charged nature of the chicoric acids contributes to poor cellular uptake, and these compounds are further plagued by rapid ester hydrolysis in vivo. To address these critical deficiencies, we designed neutral, nonhydrolyzable analogues of the chicoric acids. Herein, we report the synthesis, enzyme inhibition studies, and cellular antiviral data for a series of geminal disulfones. Of the 10 compounds evaluated, 8 showed moderate to high inhibition of IN in purified enzyme assays. The purified enzyme data correlated with antiviral assays for all but two compounds, suggesting alternative modes of inhibition. Time-of-addition studies were performed on these analogues, and the results indicate that they inhibit an early stage in the replication process, perhaps entry. In contrast, the most potent member of the correlative group shows behavior consistent with IN being the cellular target.

  DOI：

  10.1021/jm049171v

文献信息

• WO2007/65032
  申请人：——

  公开号：——

  公开（公告）日：——
• Ring substituent effects on biological activity of vinyl sulfones as inhibitors of HIV-1
  作者：D. Christopher Meadows、Tino Sanchez、Nouri Neamati、Thomas W. North、Jacquelyn Gervay-Hague

  DOI：10.1016/j.bmc.2006.10.017

  日期：2007.1

  vinyl geminal disulfone-containing compounds possessing a range of ring substituents has been synthesized to probe the impact of structure on inhibitory mechanisms. Four active compounds were identified using HIV drug susceptibility assays. Three of the inhibitors possessing either no substituents or electron-withdrawing substituents on the aromatic rings led to high levels of cytotoxicity and antiviral

  在先前的研究中，我们准备了一个小型的菊苣酸类似物文库，该文库具有强大的抗整合酶和抗病毒活性。还显示出活性化合物分为两类之一：抑制病毒复制早期的化合物和抑制病毒复制的化合物。在这项研究中，已合成了一系列具有一系列环取代基的含乙烯基双膦二砜的化合物，以探讨结构对抑制机理的影响。使用HIV药物敏感性测定法鉴定了四种活性化合物。芳香环上没有取代基或没有吸电子取代基的三种抑制剂导致高水平的细胞毒性和抗病毒活性。迷恋电子效应对活动的潜在影响，我们研究了活性化合物是否可以通过1,4-加成发生非特异性反应。为了研究该假设，将化合物与谷胱甘肽一起孵育，并通过LC / MS分析，鉴定了与单加成和双加成加合物相对应的分子离子峰。其次，我们合成了缺乏参与1，4-加成能力的类似物，并测试了它们的抗病毒活性和细胞毒性，发现该化合物对这两种活性均无活性。综上所述，本文报道的研究表明，在芳环上缺乏供电子取代基的化合物是生
• Synthesis and Biological Evaluation of Geminal Disulfones as HIV-1 Integrase Inhibitors
  作者：D. Christopher Meadows、Timothy B. Mathews、Thomas W. North、Michael J. Hadd、Chih Lin Kuo、Nouri Neamati、Jacquelyn Gervay-Hague

  DOI：10.1021/jm049171v

  日期：2005.7.1

  Integration of HIV-1 viral DNA into the host genome is carried out by HIV-integrase (IN) and is a critical step in viral replication. Although several classes of compounds have been reported to inhibit IN in enzymatic assays, inhibition is not always correlated with antiviral activity. Moreover, potent antiviral IN inhibitors such as the chicoric acids do not act upon the intended enzymatic target but behave as entry inhibitors instead. The charged nature of the chicoric acids contributes to poor cellular uptake, and these compounds are further plagued by rapid ester hydrolysis in vivo. To address these critical deficiencies, we designed neutral, nonhydrolyzable analogues of the chicoric acids. Herein, we report the synthesis, enzyme inhibition studies, and cellular antiviral data for a series of geminal disulfones. Of the 10 compounds evaluated, 8 showed moderate to high inhibition of IN in purified enzyme assays. The purified enzyme data correlated with antiviral assays for all but two compounds, suggesting alternative modes of inhibition. Time-of-addition studies were performed on these analogues, and the results indicate that they inhibit an early stage in the replication process, perhaps entry. In contrast, the most potent member of the correlative group shows behavior consistent with IN being the cellular target.