{[2-(1,3-二氧代-2,3-二氢-1H-异吲哚-2-基)乙基]硫烷基}甲氨基酰胺氢溴酸盐 | 52208-11-4

• 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
• 中文名称: {[2-(1,3-二氧代-2,3-二氢-1H-异吲哚-2-基)乙基]硫烷基}甲氨基酰胺氢溴酸盐
• 英文名称: (2-phthalimidoethyl)isothiuronium hydrobromide
• 英文别名: (2-phthalimidoethyl)isothiouronium bromide；S-(2-phthalimido-ethyl)-isothiourea; hydrobromide；S-(2-Phthalimido-aethyl)-isothioharnstoff; Hydrobromid；(2-phthalimidoethyl)isothiouronium hydrobromide；(n-phthalimidoethyl)isothiouronium hydrobromide；Pseudourea, 2-(1,3-dioxo-2-isoindolinyl)ethylthio-, hydrobromide；2-(1,3-dioxoisoindol-2-yl)ethyl carbamimidothioate;hydrobromide
• CAS: 52208-11-4
• 化学式: BrH*C₁₁H₁₁N₃O₂S
• 分子量: 330.205
• InChiKey: RULZBVGLKDQUQJ-UHFFFAOYSA-N

物化性质

• 熔点：
  229-230 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -3.91
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {[2-(1,3-二氧代-2,3-二氢-1H-异吲哚-2-基)乙基]硫烷基}甲氨基酰胺氢溴酸盐 在 盐酸 、 N-氯代丁二酰亚胺 作用下， 以 水 、 乙腈 为溶剂， 反应 0.5h， 以0.848 g的产率得到2-苯二(甲)酰亚氨基乙烷磺酰氯
  参考文献：
  名称：

  通过N-氯代琥珀酰亚胺氯磺化反应从S-烷基异硫脲盐中方便，环保地合成磺酰氯

  摘要：

  摘要 已经开发了一种方便，实用和环境友好的合成磺酰氯的方法。由S-烷基异硫脲盐以中等至优异的产率合成结构多样的磺酰氯，其可以容易地由易于获得的烷基卤化物或甲磺酸酯和廉价的硫脲通过N-氯代琥珀酰亚胺氯磺化制备。在大规模合成中，可以将来自“废水”的副产物琥珀酰亚胺与次氯酸钠（漂白剂）方便地转化为起始试剂N-氯琥珀酰亚胺，以使该方法具有可持续性。 已经开发了一种方便，实用和环境友好的合成磺酰氯的方法。由S-烷基异硫脲盐以中等至优异的产率合成结构多样的磺酰氯，其可以容易地由易于获得的烷基卤化物或甲磺酸酯和廉价的硫脲通过N-氯代琥珀酰亚胺氯磺化制备。在大规模合成中，可以将来自“废水”的副产物琥珀酰亚胺与次氯酸钠（漂白剂）方便地转化为起始试剂N-氯琥珀酰亚胺，以使该方法具有可持续性。

  DOI：

  10.1055/s-0033-1338743
• 作为产物：
  描述：

  N-(2-溴乙基)邻苯二甲酰亚胺 、 硫脲 以 乙醇 为溶剂， 反应 1.0h， 生成 {[2-(1,3-二氧代-2,3-二氢-1H-异吲哚-2-基)乙基]硫烷基}甲氨基酰胺氢溴酸盐
  参考文献：
  名称：

  通过N-氯代琥珀酰亚胺氯磺化反应从S-烷基异硫脲盐中方便，环保地合成磺酰氯

  摘要：

  摘要 已经开发了一种方便，实用和环境友好的合成磺酰氯的方法。由S-烷基异硫脲盐以中等至优异的产率合成结构多样的磺酰氯，其可以容易地由易于获得的烷基卤化物或甲磺酸酯和廉价的硫脲通过N-氯代琥珀酰亚胺氯磺化制备。在大规模合成中，可以将来自“废水”的副产物琥珀酰亚胺与次氯酸钠（漂白剂）方便地转化为起始试剂N-氯琥珀酰亚胺，以使该方法具有可持续性。 已经开发了一种方便，实用和环境友好的合成磺酰氯的方法。由S-烷基异硫脲盐以中等至优异的产率合成结构多样的磺酰氯，其可以容易地由易于获得的烷基卤化物或甲磺酸酯和廉价的硫脲通过N-氯代琥珀酰亚胺氯磺化制备。在大规模合成中，可以将来自“废水”的副产物琥珀酰亚胺与次氯酸钠（漂白剂）方便地转化为起始试剂N-氯琥珀酰亚胺，以使该方法具有可持续性。

  DOI：

  10.1055/s-0033-1338743

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] CYCLODEXTRIN DERIVATIVES AS POTENTIATORS FOR ANTIBIOTICS<br/>[FR] DÉRIVÉS DE CYCLODEXTRINE EN TANT QUE RENFORÇATEURS POUR ANTIBIOTIQUES
  申请人：PINNACLE PHARMACEUTICALS INC

  公开号：WO2009058327A1

  公开（公告）日：2009-05-07

  The invention provides a new class of antibiotics that are derivatives of cyclodextrin, which is a cyclic molecule comprising D-glucose units. In addition, the invention provides a method for potentiating the activity of antibiotic to inhibit the growth of a bacterium which is resistant to said antibiotic whereby cyclodextrin derivatives are administered with an antibiotic.

  该发明提供了一类新型抗生素，这些抗生素是环糊精衍生物，环糊精是由D-葡萄糖单元组成的环状分子。此外，该发明提供了一种增强抗生素活性以抑制对该抗生素产生耐药性的细菌生长的方法，即通过将环糊精衍生物与抗生素一起给予。
• Click synthesis of estradiol–cyclodextrin conjugates as cell compartment selective estrogens
  作者：Hye-Yeong Kim、Johann Sohn、Gihani T. Wijewickrama、Praneeth Edirisinghe、Teshome Gherezghiher、Madhubani Hemachandra、Pei-Yi Lu、R. Esala Chandrasena、Mary Ellen Molloy、Debra A. Tonetti、Gregory R.J. Thatcher

  DOI：10.1016/j.bmc.2009.11.046

  日期：2010.1

  Cyclodextrin (CD) is a well known drug carrier and excipient for enhancing aqueous solubility. CDs themselves are anticipated to have low membrane permeability because of relatively high hydrophilicity and molecular weight. CD derivatization with 17-beta estradiol (E-2) was explored extensively using a number of different click chemistries and the cell membrane permeability of synthetic CD-E-2 conjugate was explored by cell reporter assays and confocal fluorescence microscopy. In simile with reported dendrimer-E-2 conjugates, CD-E-2 was found to be a stable, extranuclear receptor selective estrogen that penetrated into the cytoplasm. (C) 2009 Elsevier Ltd. All rights reserved.
• Ryazantsev, G. B.; Shaposhnikov, A. V.; Fedoseev, V. M., Russian Journal of Organic Chemistry, 1993, vol. 29, # 11.1, p. 1777 - 1782
  作者：Ryazantsev, G. B.、Shaposhnikov, A. V.、Fedoseev, V. M.

  DOI：——

  日期：——
• 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.