diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone) | 1208998-93-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone)
• 英文别名: 1-(2-Aminoethyl)-3-[3-(methylcarbamothioylhydrazinylidene)butan-2-ylideneamino]thiourea
• CAS: 1208998-93-9
• 化学式: C₉H₁₉N₇S₂
• 分子量: 289.429
• InChiKey: HNRREDLWMLDCCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  163
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone) 、 3-(2-nitro-1H-imidazolyl)propionic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以71%的产率得到N-(6,7-dimethyl-3,10-dithioxo-2,4,5,8,9,11-hexaazatrideca-5,7-dien-13-yl)-3-(2-nitro-1H-imidazol-1-yl)propanamide
  参考文献：
  名称：

  Nitroimidazole conjugates of bis(thiosemicarbazonato)64Cu(II) – Potential combination agents for the PET imaging of hypoxia

  摘要：

  Combination agents comprising two different pharmacophores with the same biological target have the potential to show additive or synergistic activity. Bis(thiosemicarbazonato)copper(II) complexes (e.g. Cu-64-ATSM) and nitroimidazoles (e.g. F-18-MISO) are classes of tracer used for the delineation of tumor hypoxia by positron emission tomography (PET). Three nitroimidazole-bis(thiosemicarbazonato)copper(II) conjugates were produced in order to investigate their potential as combination hypoxia imaging agents. Two were derived from the known bifunctional bis(thiosemicarbazone) H(2)ATSM/A and the third from the new precursor diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone) - H(2)ATSM/en. Oxygen-dependent uptake studies were performed using the Cu-64 radiolabelled complexes in EMT6 carcinoma cells. All the complexes displayed appreciable hypoxia selectivity, with the nitroimidazole conjugates displaying greater selectivity than a simple propyl derivative used as a control. Participation of the nitroimidazole group in the trapping mechanism is indicated by the increased hypoxic uptake of the 2- vs. the 4-substituted Cu-64-ATSM/A derivatives. The 2-nitroimidazole derivative of Cu-64-ATSM/en demonstrated superior hypoxia selectivity to Cu-64-ATSM over the range of oxygen concentrations tested. Biodistribution of the radiolabelled 2-nitroimidazole conjugates was carried out in EMT6 tumor-bearing mice. The complexes showed significantly different uptake trends in comparison to each other and previously studied Cu-ATSM derivatives. Uptake of the Cu-ATSM/en conjugate in non-target organs was considerably lower than for derivatives based on Cu-ATSM/A. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2009.10.009
• 作为产物：
  描述：

  diacetyl tert-butyl 4-ethylcarbamate-4'-methylbis(thiosemicarbazone) 在 三氟乙酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 反应 1.83h， 以77%的产率得到diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone)
  参考文献：
  名称：

  Nitroimidazole conjugates of bis(thiosemicarbazonato)64Cu(II) – Potential combination agents for the PET imaging of hypoxia

  摘要：

  Combination agents comprising two different pharmacophores with the same biological target have the potential to show additive or synergistic activity. Bis(thiosemicarbazonato)copper(II) complexes (e.g. Cu-64-ATSM) and nitroimidazoles (e.g. F-18-MISO) are classes of tracer used for the delineation of tumor hypoxia by positron emission tomography (PET). Three nitroimidazole-bis(thiosemicarbazonato)copper(II) conjugates were produced in order to investigate their potential as combination hypoxia imaging agents. Two were derived from the known bifunctional bis(thiosemicarbazone) H(2)ATSM/A and the third from the new precursor diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone) - H(2)ATSM/en. Oxygen-dependent uptake studies were performed using the Cu-64 radiolabelled complexes in EMT6 carcinoma cells. All the complexes displayed appreciable hypoxia selectivity, with the nitroimidazole conjugates displaying greater selectivity than a simple propyl derivative used as a control. Participation of the nitroimidazole group in the trapping mechanism is indicated by the increased hypoxic uptake of the 2- vs. the 4-substituted Cu-64-ATSM/A derivatives. The 2-nitroimidazole derivative of Cu-64-ATSM/en demonstrated superior hypoxia selectivity to Cu-64-ATSM over the range of oxygen concentrations tested. Biodistribution of the radiolabelled 2-nitroimidazole conjugates was carried out in EMT6 tumor-bearing mice. The complexes showed significantly different uptake trends in comparison to each other and previously studied Cu-ATSM derivatives. Uptake of the Cu-ATSM/en conjugate in non-target organs was considerably lower than for derivatives based on Cu-ATSM/A. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jinorgbio.2009.10.009

文献信息

• Synthesis of sulfonamide conjugates of Cu(<scp>ii</scp>), Ga(<scp>iii</scp>), In(<scp>iii</scp>), Re(<scp>v</scp>) and Zn(<scp>ii</scp>) complexes: carbonic anhydrase inhibition studies and cellular imaging investigations
  作者：Jonathan R. Dilworth、Sofia I. Pascu、Philip A. Waghorn、Daniela Vullo、Simon R. Bayly、Martin Christlieb、Xin Sun、Claudiu T. Supuran

  DOI：10.1039/c4dt03206c

  日期：——

  of the Re complexes were prepared in good radiochemical incorporation. Inhibition of various human carbonic anhydrase isoforms (I, II, IX and XII) was tested with the ‘cold’, non-radiolabelled complexes, and compared with an acetazolamide standard (AZA). The molecular structure of a new, tri-sulfonated porphyrin-labeled sulfonamide was determined using synchrotron X-ray crystallography.

  碳酸酐酶IX（CA IX）当前引起了广泛的兴趣，将其作为肿瘤缺氧的标志物和潜在的化学治疗靶标。为了测试CA IX抑制剂可用于将PET或SPECT金属放射性同位素靶向肿瘤的原理，我们制备了许多结合芳基磺酰胺或乙酰唑酰胺衍生物的缀合物，这些衍生物与一系列铜，铟，rh，99m -tECh和锌配合物。放射性标记的“冷” Cu和一些Re配合物的64 Cu和99m Tc类似物是通过良好的放射化学掺入制备的。用“冷的”非放射性标记的复合物测试了各种人类碳酸酐酶同工型（I，II，IX和XII）的抑制作用，并与乙酰唑胺标准品（AZA）进行了比较。）。使用同步加速器X射线晶体学测定了新的三磺化卟啉标记的磺酰胺的分子结构。