(4-phthalimidobutyl)isothiuronium hydrobromide | 14122-46-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: (4-phthalimidobutyl)isothiuronium hydrobromide
• 英文别名: S-(4-phthalimido-butyl)-isothiourea; hydrobromide；S-(4-Phthalimido-butyl)-isothioharnstoff; Hydrobromid；S-(4-Phthalimido-butyl)-isothiouronium-bromid；(4-phthalimidobutyl)isothiouronium hydrobromide；4-(1,3-dioxoisoindol-2-yl)butyl carbamimidothioate;hydron;bromide
• CAS: 14122-46-4
• 化学式: BrH*C₁₃H₁₅N₃O₂S
• 分子量: 358.259
• InChiKey: WQGHDCNSCAPODD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.27
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-phthalimidobutyl)isothiuronium hydrobromide 、 2A,2B,2C,2D,2E,2F,2G,3A,3B,3C,3D,3E,3F,3G-tetradeca-O-acetyl-6A,6B,6C,6D,6E,6F,6G-heptaiodo-6A,6B,6C,6D,6E,6F,6G-heptadeoxy-β-cyclodextrin 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以24%的产率得到heptakis[2,3-di-O-acetyl-6-deoxy-6-(4-phthalimidobutylthio)]cyclomaltoheptaose
  参考文献：
  名称：

  β-Cyclodextrin derivatives that inhibit anthrax lethal toxin

  摘要：

  Recently, we demonstrated that simultaneous blocking of bacteria] growth by antibiotics and inhibition of anthrax toxin action with antibodies against protective antigen were beneficial for the treatment of anthrax. The present study examined the hypothesis that blocking the pore formed by protective antigen can inhibit the action of anthrax toxin. The potential inhibitors were chosen by a structure-based design using beta-cyclodextrin as the starting molecule. Several beta-cycloclextrin derivatives were evaluated for their ability to protect RAW 264.7 cells from the action of anthrax lethal toxin. Per-substituted aminoalkyl derivatives displayed inhibitory activity and were protective against anthrax lethal toxin action at low microinolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates For anthrax treatment. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.054
• 作为产物：
  描述：

  N-(4-溴丁基)邻苯二甲酰亚胺 、 硫脲 以 乙醇 为溶剂， 生成 (4-phthalimidobutyl)isothiuronium hydrobromide
  参考文献：
  名称：

  Search for Cyclodextrin-Based Inhibitors of Anthrax Toxins: Synthesis, Structural Features, and Relative Activities

  摘要：

  摘要 最近，我们利用结构启发药物设计证明，β-环糊精的氨基烷基衍生物通过阻断炭疽毒素的保护性抗原（PA）亚基形成的跨膜孔来抑制炭疽致死毒素的作用。在本研究中，我们评估了一系列新的β-环糊精衍生物，目的是确定炭疽毒素的强效抑制剂。我们测试了新合成的具有不同长度烷基间隔的 β-环糊精庚-6-硫代氨基烷基和庚-6-硫代胍基烷基衍生物抑制细胞中致死毒素的细胞毒性以及阻断通过在平面双层脂膜中重建的 PA 通道的离子传导的能力。大多数受试衍生物在低浓度或亚摩尔浓度下对炭疽致死毒素的作用具有保护作用。它们还能在低至 0.1 nM 的浓度下阻断 PA 通道的离子传导。研究发现，这些衍生物在细胞保护和通道阻断方面的活性取决于取代基团的长度和化学性质。其中一种化合物还能阻断水肿毒素的活性。希望这些结果将有助于确定一类新的炭疽治疗药物，即阻断毒素转运到细胞膜的途径--PA 通道的药物。

  DOI：

  10.1128/aac.00693-06

文献信息

• Search for Cyclodextrin-Based Inhibitors of Anthrax Toxins: Synthesis, Structural Features, and Relative Activities
  作者：Vladimir A. Karginov、Ekaterina M. Nestorovich、Adiamseged Yohannes、Tanisha M. Robinson、Nour Eddine Fahmi、Frank Schmidtmann、Sidney M. Hecht、Sergey M. Bezrukov

  DOI：10.1128/aac.00693-06

  日期：2006.11

  Recently, using structure-inspired drug design, we demonstrated that aminoalkyl derivatives of β-cyclodextrin inhibited anthrax lethal toxin action by blocking the transmembrane pore formed by the protective antigen (PA) subunit of the toxin. In the present study, we evaluate a series of new β-cyclodextrin derivatives with the goal of identifying potent inhibitors of anthrax toxins. Newly synthesized hepta-6-thioaminoalkyl and hepta-6-thioguanidinoalkyl derivatives of β-cyclodextrin with alkyl spacers of various lengths were tested for the ability to inhibit cytotoxicity of lethal toxin in cells as well as to block ion conductance through PA channels reconstituted in planar bilayer lipid membranes. Most of the tested derivatives were protective against anthrax lethal toxin action at low or submicromolar concentrations. They also blocked ion conductance through PA channels at concentrations as low as 0.1 nM. The activities of the derivatives in both cell protection and channel blocking were found to depend on the length and chemical nature of the substituent groups. One of the compounds was also shown to block the edema toxin activity. It is hoped that these results will help to identify a new class of drugs for anthrax treatment, i.e., drugs that block the pathway for toxin translocation into the cytosol, the PA channel.

  摘要 最近，我们利用结构启发药物设计证明，β-环糊精的氨基烷基衍生物通过阻断炭疽毒素的保护性抗原（PA）亚基形成的跨膜孔来抑制炭疽致死毒素的作用。在本研究中，我们评估了一系列新的β-环糊精衍生物，目的是确定炭疽毒素的强效抑制剂。我们测试了新合成的具有不同长度烷基间隔的 β-环糊精庚-6-硫代氨基烷基和庚-6-硫代胍基烷基衍生物抑制细胞中致死毒素的细胞毒性以及阻断通过在平面双层脂膜中重建的 PA 通道的离子传导的能力。大多数受试衍生物在低浓度或亚摩尔浓度下对炭疽致死毒素的作用具有保护作用。它们还能在低至 0.1 nM 的浓度下阻断 PA 通道的离子传导。研究发现，这些衍生物在细胞保护和通道阻断方面的活性取决于取代基团的长度和化学性质。其中一种化合物还能阻断水肿毒素的活性。希望这些结果将有助于确定一类新的炭疽治疗药物，即阻断毒素转运到细胞膜的途径--PA 通道的药物。
• [EN] ß-CYCLODEXTRIN DERIVATIVES AND THEIR USE AGAINST ANTHRAX LETHAL TOXIN<br/>[FR] DERIVES DE $G(B)-CYCLODEXTRINE, ET LEUR UTILISATION CONTRE LA TOXINE LETALE DE L'ANTHRAX
  申请人：PINNACLE PHARMACEUTICALS

  公开号：WO2006001844A3

  公开（公告）日：2006-10-19
• β-Cyclodextrin derivatives that inhibit anthrax lethal toxin
  作者：Vladimir A. Karginov、Adiamseged Yohannes、Tanisha M. Robinson、Nour Eddine Fahmi、Kenneth Alibek、Sidney M. Hecht

  DOI：10.1016/j.bmc.2005.07.054

  日期：2006.1

  Recently, we demonstrated that simultaneous blocking of bacteria] growth by antibiotics and inhibition of anthrax toxin action with antibodies against protective antigen were beneficial for the treatment of anthrax. The present study examined the hypothesis that blocking the pore formed by protective antigen can inhibit the action of anthrax toxin. The potential inhibitors were chosen by a structure-based design using beta-cyclodextrin as the starting molecule. Several beta-cycloclextrin derivatives were evaluated for their ability to protect RAW 264.7 cells from the action of anthrax lethal toxin. Per-substituted aminoalkyl derivatives displayed inhibitory activity and were protective against anthrax lethal toxin action at low microinolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates For anthrax treatment. (c) 2005 Elsevier Ltd. All rights reserved.