10-(4-bromobutyl)-3,6-bis(dimethylamino)acridinium bromide | 1280225-51-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 10-(4-bromobutyl)-3,6-bis(dimethylamino)acridinium bromide
• 英文别名: 10-(4-bromobutyl)-3-N,3-N,6-N,6-N-tetramethylacridin-10-ium-3,6-diamine;bromide
• CAS: 1280225-51-5
• 化学式: Br*C₂₁H₂₇BrN₃
• 分子量: 481.273
• InChiKey: NOKSGIVJXQBXIU-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.59
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  10.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  10-(4-bromobutyl)-3,6-bis(dimethylamino)acridinium bromide 在 magnesium sulfate 、 potassium carbonate 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.17h， 生成 3,6-bis(dimethylamino)-10-(4-(2-((phenethylimino)methyl)-1H-imidazol-1-yl)butyl)acridinium
  参考文献：
  名称：

  Metal Complex Mediated Conjugation of Peptides to Nucleus Targeting Acridine Orange: A Modular Concept for Dual-Modality Imaging Agents

  摘要：

  To target the nucleus of specific cells, trifunctional radiopharmaceuticals are required. We have synthesized acridine orange derivatives which comprise an imidazole-2-carbaldehyde function for coordination to the [Re(CO)(3)](+) or [(99)mTc(CO)(3)](+) core. Upon coordination, this aldehyde is activated and rapidly forms imines with amines from biological molecules. This metal-mediated imine formation allows for the conjugation of a nuclear targeting portion with a specific cell receptor binding function directly on the metal. With this concept, we have conjugated the acridine orange part to a bombesin peptide directly on the Tc-99m core and in one step. In addition, a linker containing an integrated disulfide has been coupled to bombesin. LC/MS study showed that the disulfide was reductively cleaved with a 60 min half-life time. This concept enables the combination of a nucleus targeting agent with a specific cell receptor molecule directly on the metal without the need of separate conjugation prior to labeling, thus, a modular approach. High uptake of the BBN conjugate into PC-3 cells was detected by fluorescence microscopy, whereas uptake into B16BL6 cells was negligible.

  DOI：

  10.1021/bc2000269
• 作为产物：
  描述：

  1,4-二溴丁烷 、 吖啶橙 以 甲苯 为溶剂， 反应 24.0h， 以77%的产率得到10-(4-bromobutyl)-3,6-bis(dimethylamino)acridinium bromide
  参考文献：
  名称：

  Trifunctional^99mTc based radiopharmaceuticals: metal-mediated conjugation of a peptide with a nucleus targeting intercalator

  摘要：

  多功能分子成像剂的发展已成为放射性药物化学的主要趋势。本文介绍了三功能化合物的合成，这些化合物结合了以吖啶橙（AO）为基础的插入剂和GRP受体特异性类似bombesin的肽（BBN）。通过[2 + 1]方法，将这两种功能与第三种功能[M(CO)3]+（M = 99mTc，Re）部分进行金属介导的连接，得到了最终的三功能分子。作为核靶向剂，吖啶橙具有强烈的荧光，衍生化为双齿配体4-咪唑羧酸酯，bombesin则带有异氰基作为单齿配体。为了研究细胞和核摄取，我们合成了并表征了[Re(L1-BBN)(L2-Ical)(CO)3]型配合物。为了放射性药物的目的，我们采用逐步合成法合成了99mTc类似物。对携带BBN受体的PC-3细胞进行荧光显微镜研究，结果显示细胞质中的摄取率高且迅速。对于缺乏BBN肽的双功能分子，未观察到内化现象。

  DOI：

  10.1039/c0ob00504e

文献信息

• Trifunctional^99mTc based radiopharmaceuticals: metal-mediated conjugation of a peptide with a nucleus targeting intercalator
  作者：Karel Zelenka、Lubor Borsig、Roger Alberto

  DOI：10.1039/c0ob00504e

  日期：——

  The development of molecular imaging agents with multiple functions has become a major trend in radiopharmaceutical chemistry. We present herein the syntheses of trifunctional compounds, combining an acridine orange (AO) based intercalator with a GRP receptor specific bombesin like peptide (BBN). Metal-mediated conjugation of these two functions via the [2 + 1] approach to the third function, the [M(CO)3]+ (M = 99mTc, Re) moiety, yielded the final trifunctional molecules. The strongly fluorescent acridine orange, a nuclear targeting agent, has been derivatised with 4-imidazolecarboxylate as a bidentate ligand and bombesin with an isonitrile group as a monodentate ligand. For cell and nuclear uptake studies, [Re(L1-BBN)(L2-Ical)(CO)3] type complexes were synthesized and characterized. For radiopharmaceutical purposes, the 99mTc analogues have been prepared in a stepwise synthesis. Fluorescence microscopy studies on PC-3 cells, bearing the BBN receptor, showed high and rapid uptake into the cytoplasm. For the bifunctional molecule, lacking the BBN peptide, no internalization was observed.

  多功能分子成像剂的发展已成为放射性药物化学的主要趋势。本文介绍了三功能化合物的合成，这些化合物结合了以吖啶橙（AO）为基础的插入剂和GRP受体特异性类似bombesin的肽（BBN）。通过[2 + 1]方法，将这两种功能与第三种功能[M(CO)3]+（M = 99mTc，Re）部分进行金属介导的连接，得到了最终的三功能分子。作为核靶向剂，吖啶橙具有强烈的荧光，衍生化为双齿配体4-咪唑羧酸酯，bombesin则带有异氰基作为单齿配体。为了研究细胞和核摄取，我们合成了并表征了[Re(L1-BBN)(L2-Ical)(CO)3]型配合物。为了放射性药物的目的，我们采用逐步合成法合成了99mTc类似物。对携带BBN受体的PC-3细胞进行荧光显微镜研究，结果显示细胞质中的摄取率高且迅速。对于缺乏BBN肽的双功能分子，未观察到内化现象。
• Metal Complex Mediated Conjugation of Peptides to Nucleus Targeting Acridine Orange: A Modular Concept for Dual-Modality Imaging Agents
  作者：Karel Zelenka、Lubor Borsig、Roger Alberto

  DOI：10.1021/bc2000269

  日期：2011.5.18

  To target the nucleus of specific cells, trifunctional radiopharmaceuticals are required. We have synthesized acridine orange derivatives which comprise an imidazole-2-carbaldehyde function for coordination to the [Re(CO)(3)](+) or [(99)mTc(CO)(3)](+) core. Upon coordination, this aldehyde is activated and rapidly forms imines with amines from biological molecules. This metal-mediated imine formation allows for the conjugation of a nuclear targeting portion with a specific cell receptor binding function directly on the metal. With this concept, we have conjugated the acridine orange part to a bombesin peptide directly on the Tc-99m core and in one step. In addition, a linker containing an integrated disulfide has been coupled to bombesin. LC/MS study showed that the disulfide was reductively cleaved with a 60 min half-life time. This concept enables the combination of a nucleus targeting agent with a specific cell receptor molecule directly on the metal without the need of separate conjugation prior to labeling, thus, a modular approach. High uptake of the BBN conjugate into PC-3 cells was detected by fluorescence microscopy, whereas uptake into B16BL6 cells was negligible.