N-[3-chloro-3-methyl-1-(2-nitroimidazol-1-yl)butan-2-ylidene]hydroxylamine | 159564-10-0

• 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: N-[3-chloro-3-methyl-1-(2-nitroimidazol-1-yl)butan-2-ylidene]hydroxylamine
• CAS: 159564-10-0
• 化学式: C₈H₁₁ClN₄O₃
• 分子量: 246.653
• InChiKey: SVWSBXHVWKLNQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  96.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[3-chloro-3-methyl-1-(2-nitroimidazol-1-yl)butan-2-ylidene]hydroxylamine 、 1,3-丙二胺 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 以51%的产率得到N-[3-[3-[[3-hydroxyimino-2-methyl-4-(2-nitroimidazol-1-yl)butan-2-yl]amino]propylamino]-3-methyl-1-(2-nitroimidazol-1-yl)butan-2-ylidene]hydroxylamine
  参考文献：
  名称：

  Effect of a second nitroimidazole redox centre on the accumulation of a hypoxia marker: Synthesis and in vitro evaluation of 99mTc-labeled bisnitroimidazole propylene amine oxime complexes

  摘要：

  Up to now, most of the hypoxia markers contain only one nitroimidazole redox centre, such as Oxo[[3,3,9,9-tetramethyl-1-(2-nitro-1H-imidazol-1-yl)-4,8-diazaundecane-2,10-dione dioximato] (3-)-N, N', N '', N''']technetium (Tc-99m-1, BMS181321). Introducing a second nitroimidazole redox centre may enhance the hypoxic accumulation of the markers. In the present work, four Tc-99m-1 (BMS181321, containing one 2-nitroimidazole) analogues, that is, Tc-99m-2 (containing two 2-nitroimidazoles), Tc-99m-3 (containing one 4-nitroimidazole), Tc-99m-4 (containing two 4-nitroimidazoles) and Tc-99m-5 (containing both a 2-nitroimidazole and a 4-nitroimidazole) were synthesized, and the hypoxic accumulation was evaluated in vitro using murine sarcoma S180 cells. Tc-99m-3 and Tc-99m-4 displayed no significant anoxic/normoxic differentials, whereas Tc-99m-1 (BMS181321), Tc-99m-2 and Tc-99m-5 showed high anoxic cellular uptakes. The anoxic uptake of Tc-99m-2 reached up to 59.0 +/- 0.9% at 4 h, which was 2.4 times as that of Tc-99m-1. Tc-99m-2 displayed high hypoxic accumulation, indicating that introducing a second nitroimidazole redox centre, that is, 2-nitroimidazole, affected the hypoxic accumulation. Consequently, Tc-99m-2 may serve as a viable candidate for hypoxia marker. This finding may eventually lead to the development of compounds containing multi-redox centres as hypoxia markers. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.042
• 作为产物：
  描述：

  1-溴-3-甲基-2-丁烯 在 盐酸 、 potassium carbonate 作用下， 生成 N-[3-chloro-3-methyl-1-(2-nitroimidazol-1-yl)butan-2-ylidene]hydroxylamine
  参考文献：
  名称：

  Synthesis and radiolabeling of 64Cu-labeled 2-nitroimidazole derivative 64Cu-BMS2P2 for hypoxia imaging

  摘要：

  The objective of this study was to develop a positron emission tomography (PET) probe with hypoxia targeting specificity and a relatively long half-life. The synthesis, Cu-64-labeling in vitro and in vivo study of the novel 2-nitroimidazole complex Cu-64-BMS2P2 is presented in this study. The hypoxia targeting capacity of Cu-64-BMS2P2 in vitro was evaluated and compared with the Cu-64-BMS181321, and confirmed by PET imaging in vivo and immunohistochemistry for carbonic anhydrase 9 (CA9) in a tumor mouse model. These results suggest that Cu-64-BMS2P2 is a promising candidate for PET hypoxia imaging and worthy of further investigations in dynamic hypoxia imaging. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.01.077

文献信息

• METAL-OXIME CHELATES FOR USE AS RADIOPHARMACEUTICAL AGENTS
  申请人：Nycomed Amersham PLC

  公开号：EP0663900B1

  公开（公告）日：1999-09-22
• US5993774A
  申请人：——

  公开号：US5993774A

  公开（公告）日：1999-11-30
• [EN] RADIOMETAL COMPLEXES THAT LOCALISE IN HYPOXIC TISSUE<br/>[FR] COMPLEXES RADIOMETALLIQUES SE FIXANT DANS LES TISSUS HYPOXIQUES
  申请人：——

  公开号：WO1995004552A2

  公开（公告）日：1995-02-16

  [EN] The invention concerns ligands, e.g. based on alkylene amine oxime particularly butylene amine oxime ring structures, and radiometal complexes thereof. The radiometal complexes are intrinsically capable of localising in tumours or hypoxic tissue and can be used in imaging or radiotherapy.
  [FR] L'invention concerne des ligands, par exemple ceux à base d'alkylène amine oxime et notamment de structures cycliques de butylène amine oxime, ainsi que certains de leurs complexes radiométalliques. Ces derniers offrent la capacité intrinsèque de se fixer dans des tumeurs ou des tissus hypoxiques et on peut les utiliser pour l'imagerie ou la radiothérapie.