10-bromodecyl-tetra-O-benzoyl-β-D-glucopyranoside | 382607-66-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 10-bromodecyl-tetra-O-benzoyl-β-D-glucopyranoside
• 英文别名: [(2R,3R,4S,5R,6R)-3,4,5-tribenzoyloxy-6-(10-bromodecoxy)oxan-2-yl]methyl benzoate
• CAS: 382607-66-1
• 化学式: C₄₄H₄₇BrO₁₀
• 分子量: 815.755
• InChiKey: BQFDLHUBEQTZEU-GDJDUYBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.7
• 重原子数：
  55
• 可旋转键数：
  24
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  10-bromodecyl-tetra-O-benzoyl-β-D-glucopyranoside 在 盐酸 、 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 乙酸乙酯 、 乙腈 为溶剂， 反应 100.5h， 生成
  参考文献：
  名称：

  [EN] RADIOPHARMACEUTICAL CONJUGATE OF A METABOLITE AND AN EPR AGENT, FOR TARGETING TUMOUR CELLS
  [FR] CONJUGUÉS RADIOPHARMACEUTIQUES

  摘要：

  公开号：

  WO2016046793A3
• 作为产物：
  描述：

  a-无水葡萄糖酯 在 吡啶 、 六甲基二硅烷 、 碘 、 zinc(II) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 10-bromodecyl-tetra-O-benzoyl-β-D-glucopyranoside
  参考文献：
  名称：

  开发靶向白蛋白结合放射性配体：合成、放射性标记和初步体内研究

  摘要：

   介绍 该化合物命名为4-[10-(4-(2,5-二氧代-2,5-二氢-1H-吡咯-1-基)丁酰胺基)癸基]-11-[10-(β, d- glucopyranos-1) -yl)-1-氧代癸基]-1,4,8,11-四氮杂环十四烷-1,8-二乙酸是一种新合成的分子，能够在体内与白蛋白结合形成生物缀合物。该化合物被命名为GluCAB（葡萄糖-螯合剂-白蛋白-结合剂）-马来酰亚胺-1 。放射性标记的 GluCAB-maleimide -1和随后的生物缀合物被提议用于前瞻性肿瘤学应用，并通过“增强渗透性和保留（EPR）效应”和葡萄糖代谢研究肿瘤定位的理论双靶向原理。  方法 前体 GluCAB-amine- 2和随后的 GluCAB-maleimide- 1是通过cyclam 模板的连续区域选择性、远端 N 功能化合成的，该模板带有含有合成衍生的 β-葡萄糖苷的系链，随后是第二个连接体以掺入马来酰亚胺白蛋白结合部分。

  DOI：

  10.1016/j.nucmedbio.2021.01.001

文献信息

• <i>In Vivo</i> Albumin‐Binding of a <i>C</i> ‐Functionalized Cyclam Platform for ⁶⁴ Cu‐PET/CT Imaging in Breast Cancer Model
  作者：Thomas Le Bihan、Cathryn H. S. Driver、Thomas Ebenhan、Nathalie Le Bris、Jan Rijn Zeevaart、Raphaël Tripier

  DOI：10.1002/cmdc.202000800

  日期：2021.3.3

  (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64Cu]Cu‐GluCAB‐2Mal and previous‐generation [64Cu]Cu‐GluCAB‐1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64Cu]Cu‐GluCAB‐2Mal was clearly evident with twice as much accumulation

  已经合成并研究了改进的葡萄糖螯合剂白蛋白生物缀合物 (GluCAB) 衍生物 GluCAB-2 Mal及其第一代类似物 GluCAB-1 Mal用于乳腺癌小鼠模型的体内 64 Cu-PET/CT 成像。放射性配体通过增强通透性和保留 (EPR) 效应实现肿瘤靶向，并通过葡萄糖代谢发挥支持作用。[ 64 Cu]Cu-GluCAB-2 Mal (99 % RCP) 表现出高血清稳定性，可立即与血清蛋白结合。[ 64 Cu]Cu-GluCAB-2 Mal与上一代肿瘤靶向比较的体内实验64 Cu]Cu-GluCAB-1 Mal包括同种异体移植 E0771 乳腺癌小鼠模型中的 microPET/CT 成像和生物分布分析。[ 64 Cu]Cu-GluCAB-2 Mal 的肿瘤吸收明显明显，其积累量是其前身的两倍，24 小时后肿瘤/肌肉比高达 5。进一步的比较表明 [ 64 Cu]Cu-Glu-CAB-2
• Radiopharmaceutical conjugate of a metabolite and an EPR agent, for targeting tumour cells
  申请人：The South African Nuclear Energy Corporation Limited

  公开号：US10874753B2

  公开（公告）日：2020-12-29

  This invention relates new radiopharmaceutical conjugates for use in improved methods of diagnosis and treatment of cancer. The radiopharmaceutical conjugate comprises, in sequence: a metabolite that targets tumour cells, bound to a chelating agent capable of containing a radionuclide, bound to a linker capable of binding with an EPR agent in vitro or in vivo; or a chelating agent capable of containing a radionuclide, bound to a metabolite that targets tumour cells, bound to a linker capable of binding with an EPR agent in vitro or in vivo. The radiopharmaceutical conjugates of the present invention provide active and passive targeted radio nuclide delivery systems that can help to improve the biodistribution and pharmacological toxicity of the radiopharmaceuticals used for the diagnosis and therapy of cancer.

  本发明涉及用于改进癌症诊断和治疗方法的新型放射性药物共轭物。放射性药物共轭物依次包括：一种靶向肿瘤细胞的代谢物，与一种能够包含放射性核素的螯合剂结合，与一种能够在体外或体内与 EPR 制剂结合的连接体结合；或一种能够包含放射性核素的螯合剂，与一种靶向肿瘤细胞的代谢物结合，与一种能够在体外或体内与 EPR 制剂结合的连接体结合。本发明的放射性药物共轭物提供了主动和被动的靶向放射性核素递送系统，有助于改善用于诊断和治疗癌症的放射性药物的生物分布和药理毒性。
• Monosaccharide-Linked Inhibitors of <i>O</i>⁶-Methylguanine-DNA Methyltransferase (MGMT):  Synthesis, Molecular Modeling, and Structure−Activity Relationships
  作者：Jost Reinhard、William E. Hull、Claus-Wilhelm von der Lieth、Uta Eichhorn、Hans-Christian Kliem、Bernd Kaina、Manfred Wiessler

  DOI：10.1021/jm010006e

  日期：2001.11.1

  A series of potential inhibitors of the human DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) were synthesized, characterized in detail by NMR, and tested for their ability to deplete MGMT activity in vitro. The new compounds, omega-[O-6-R-guan-9-yl]-(CH2)(n)-beta -d-glucosides with R = benzyl or 4-bromothenyl and omega = n = 2, 4, ... 12, were compared with the established inhibitors O-6 -benzylguanine (O-6-BG), 8-aza-O-6-benzylguanine (8-aza-BG), and O-6-(4-bromothenyl)guanine (4-BTG), which exhibit in an in vitro assay IC50 values of 0.62, 0.038, and 0.009 muM, respectively. Potential advantages of the glucosides are improved water solubility and selective uptake in tumor cells. The 4-BTG glucosides with n = 2, 4, 6 show moderate inhibition with an IC50 of ca. 0.5 muM, while glucosides derived from BG and 8-aza-BG showed significantly poorer inhibition compared to the parent compounds. The 4-BTG glucosides with n = 8, 10, 12 were effective inhibitors with IC50 values of ca. 0.03 muM. To understand this behavior, extensive molecular modeling studies were performed using the published crystal structure of MGMT (PDB entry: 1QNT). The inhibitor molecules were docked into the BG binding pocket, and molecular dynamics simulations with explicit water molecules were carried out. Stabilization energies for the interactions of specific regions of the inhibitor and individual amino acid residues were calculated. The alkyl spacer is located in a cleft along helix 6 of MGMT. With increasing spacer length there is increasing interaction with several amino acid residues which play an important role in the proposed nucleotide flipping mechanism required for DNA repair.
• RADIOPHARMACEUTICAL CONJUGATE
  申请人：The South African Nuclear Energy Corporation Limited

  公开号：US20170296684A1

  公开（公告）日：2017-10-19

  This invention relates new radiopharmaceutical conjugates for use in improved methods of diagnosis and treatment of cancer. The radiopharmaceutical conjugate comprises, in sequence: a metabolite that targets tumour cells, bound to a chelating agent capable of containing a radionuclide, bound to a linker capable of binding with an EPR agent in vitro or in vivo; or a chelating agent capable of containing a radionuclide, bound to a metabolite that targets tumour cells, bound to a linker capable of binding with an EPR agent in vitro or in vivo. The radiopharmaceutical conjugates of the present invention provide active and passive targeted radio nuclide delivery systems that can help to improve the biodistribution and pharmacological toxicity of the radiopharmaceuticals used for the diagnosis and therapy of cancer.