1-α-D-(6-((8,9E)-9-(2-nitro-1H-imidazol-1-yl)allyloxy)methyl)glucopyranose | 1383737-07-2

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 1-α-D-(6-((8,9E)-9-(2-nitro-1H-imidazol-1-yl)allyloxy)methyl)glucopyranose
• 英文别名: (2S,3R,4S,5S,6R)-6-[[(E)-3-(2-nitroimidazol-1-yl)prop-2-enoxy]methyl]oxane-2,3,4,5-tetrol
• CAS: 1383737-07-2
• 化学式: C₁₂H₁₇N₃O₈
• 分子量: 331.282
• InChiKey: BPSQLAAFDMNNNB-TUPIVGSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-(1,2,3,4-tetra-O-acetyl)-6-(((8,9E)-9-(2-nitro-1H-imidazol-1-yl)allyloxy)methyl)glucopyranose 在 甲醇 、 sodium hydroxide 作用下， 反应 0.33h， 生成 1-α-D-(6-((8,9E)-9-(2-nitro-1H-imidazol-1-yl)allyloxy)methyl)glucopyranose 、 1-β-D-(6-((8,9E)-9-(2-nitro-1H-imidazol-1-yl)allyloxy)methyl)glucopyranose
  参考文献：
  名称：

  Design, Synthesis, and Preliminary Biological Evaluation of 6-O-Glucose–Azomycin Adducts for Diagnosis and Therapy of Hypoxic Tumors

  摘要：

  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.

  DOI：

  10.1021/jm2017336

文献信息

• 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.