1-(1,2,3,4-Tetra-O-acetyl)-6-O-(9-[2-nitro-1H-imidazolyl]-8-O-(4-nitrobenzenesulfonyloxy)propyl)glucopyranose | 1232866-22-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(1,2,3,4-Tetra-O-acetyl)-6-O-(9-[2-nitro-1H-imidazolyl]-8-O-(4-nitrobenzenesulfonyloxy)propyl)glucopyranose
• 英文别名: (3R,4S,5R,6R)-6-((3-(2-nitro-1H-imidazol-1-yl)-2-(4-nitrophenylsulfonyloxy)propoxy)methyl)tetrahydro-2H-pyran-2,3,4,5-tetrayl tetraacetate；[(2R,3R,4S,5R)-4,5,6-triacetyloxy-2-[[3-(2-nitroimidazol-1-yl)-2-(4-nitrophenyl)sulfonyloxypropoxy]methyl]oxan-3-yl] acetate
• CAS: 1232866-22-6
• 化学式: C₂₆H₃₀N₄O₁₇S
• 分子量: 702.607
• InChiKey: BEIWTIZWXHABCA-FGODVSHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  48
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  285
• 氢给体数：
  0
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  1-(1,2,3,4-Tetra-O-acetyl)-6-O-(9-[2-nitro-1H-imidazolyl]-8-O-(4-nitrobenzenesulfonyloxy)propyl)glucopyranose 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 以28%的产率得到1-(1,2,3,4-tetra-O-acetyl)-6-(((8,9E)-9-(2-nitro-1H-imidazol-1-yl)allyloxy)methyl)glucopyranose
  参考文献：
  名称：

  [EN] COMPOUNDS USEFUL IN DELIVERING ANTI-NEOPLASTIC THERAPY AND DIAGNOSTIC IMAGING TO HYPOXIC CELLS AND METHODS OF USE THEREOF
  [FR] COMPOSÉS UTILES DANS L'ADMINISTRATION D'UNE THÉRAPIE ANTINÉOPLASIQUE ET EN IMAGERIE DIAGNOSTIQUE DE CELLULES HYPOXIQUES ET PROCÉDÉS POUR LES UTILISER

  摘要：

  公开号：

  WO2010073126A3
• 作为产物：
  描述：

  methyl-1-α-D-(2,3,4-tri-O-benzyl)-6-O-(9-[2-nitro-1H-imidazolyl]-8-O-(4-nitrobenzenesulfonyloxy)propyl)glucopyranose 、 乙酸酐 在 三氟甲磺酸三甲基硅酯 作用下， 以36%的产率得到1-(1,2,3,4-Tetra-O-acetyl)-6-O-(9-[2-nitro-1H-imidazolyl]-8-O-(4-nitrobenzenesulfonyloxy)propyl)glucopyranose
  参考文献：
  名称：

  [EN] COMPOUNDS USEFUL IN DELIVERING ANTI-NEOPLASTIC THERAPY AND DIAGNOSTIC IMAGING TO HYPOXIC CELLS AND METHODS OF USE THEREOF
  [FR] COMPOSÉS UTILES DANS L'ADMINISTRATION D'UNE THÉRAPIE ANTINÉOPLASIQUE ET EN IMAGERIE DIAGNOSTIQUE DE CELLULES HYPOXIQUES ET PROCÉDÉS POUR LES UTILISER

  摘要：

  公开号：

  WO2010073126A3

文献信息

• Synthesis and Biological Evaluation of Iodoglucoazomycin (I-GAZ), an Azomycin-Glucose Adduct with Putative Applications in Diagnostic Imaging and Radiotherapy of Hypoxic Tumors
  作者：Piyush Kumar、Hassan R. H. Elsaidi、Bohdarianna Zorniak、Evelyn Laurens、Jennifer Yang、Veena Bacchu、Monica Wang、Leonard I. Wiebe

  DOI：10.1002/cmdc.201600213

  日期：2016.8.5

  Iodoglucoazomycin (I-GAZ; N-(2-iodo-3-(6-O-glucosyl)propyl)-2-nitroimidazole), a non-glycosidic nitroimidazole-6-O-glucose adduct, was synthesized, radioiodinated, and evaluated as a substrate of glucose transporter 1 (GLUT1) for radiotheranostic (therapy+diagnostic) management of hypoxic tumors. Nucleophilic iodination of the nosylate synthon of I-GAZ followed by deprotection afforded I-GAZ in 74 %

  合成了非糖苷的硝基咪唑-6-O-葡萄糖加合物碘葡糖霉素（I-GAZ； N-（2-碘-3-（6-O-葡糖基）丙基）-2-硝基咪唑），进行了放射性碘化并评估作为葡萄糖转运蛋白1（GLUT1）的底物，用于低氧性肿瘤的放射线治疗（治疗+诊断）。I-GAZ的nosylate合成子的亲核碘化，然后脱保护，以74％的总收率得到I-GAZ。使用[（123/131）I]碘化物（50-70％RCY）通过“交换”标记对I-GAZ进行放射性碘标记，然后通过SEp-Pak™（> 96％RCP）纯化。[（131）I] I-GAZ在无菌水中的2％乙醇溶液中稳定保存14天，可保存14天。在细胞培养中，发现I-GAZ在浓度<0.5 mm时对EMT-6细胞无毒，并且对放射敏感性较弱（在EMT-6细胞存活率为10％时SER 1.1;在0时为1.2。在MCF-7细胞中存活率为1％）。EMT-6细胞中[（123）I] I-GAZ的低氧/高氧摄取比在2小时时为1
• Design, Synthesis, and Preliminary Biological Evaluation of 6-<i>O</i>-Glucose–Azomycin Adducts for Diagnosis and Therapy of Hypoxic Tumors
  作者：Piyush Kumar、Gennady Shustov、Hong Liang、Vladimir Khlebnikov、Weizhong Zheng、Xiao-Hong Yang、Chris Cheeseman、Leonard I. Wiebe

  DOI：10.1021/jm2017336

  日期：2012.7.12

  Several 2-nitroimidazole-based molecules (NIs) are used as clinical hypoxic tumor radiodiagnostics, but they are not effective as radiosensitizers/radiochemotherapeutics. These NIs permeate tumor cells nonselectively via diffusion, and in therapy, where high doses are required, their dose limiting toxicities preclude success. The synthesis and preliminary in vitro evaluations of three glucoazomycins, members of a novel class of C6-O-glucose-linked-azomycin conjugates that are putative substrates of glucose transport proteins (GLUTs) and possess hypoxia-selective radiosensitization features, are now reported. The hypoxia-dependent upregulation of several GLUTs provides a rational basis to develop these glucoazomycins because more selective uptake in hypoxic cells would decrease systemic toxicities at effective doses. Calculated partition coefficients (ClogP, -1.70 to -2.99) predict rapid in vivo clearance for low systemic toxicity. In vitro experimental data show that glucoazomycins are radiosensitizers and that they competitively inhibit glucose uptake.