tert-butyl 2-(2-nitro-1H-imidazol-1-yl)acetate | 127894-74-0

• 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: tert-butyl 2-(2-nitro-1H-imidazol-1-yl)acetate
• 英文别名: tert-butyl 2-(2-nitroimidazol-1-yl)acetate；tert-butyl (2-nitro-imidazol-1-yl)acetate；tert-butyl-(2-nitro-imidazol-1-yl)acetate
• CAS: 127894-74-0
• 化学式: C₉H₁₃N₃O₄
• 分子量: 227.22
• InChiKey: WUOFFGDZUYMRFU-UHFFFAOYSA-N

物化性质

• 沸点：
  378.0±44.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  89.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(2-nitro-1H-imidazol-1-yl)acetate 在 4-二甲氨基吡啶 、 茴香硫醚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 48.0h， 生成 2-(2-nitro-imidazol-1-yl)-N-(4-sulfamoylbenzyl)acetamide
  参考文献：
  名称：

  Hypoxia-Targeting Carbonic Anhydrase IX Inhibitors by a New Series of Nitroimidazole-Sulfonamides/Sulfamides/Sulfamates

  摘要：

  A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on the complex of hCA II with the lead sulfamide derivative of this series clarified the binding mode of this type of inhibitors in the enzyme active site cavity. Some of the best nitroimidazole CA IX inhibitors showed significant activity in vitro by reducing hypoxia-induced extracellular acidosis in HT-29 and HeLa cell lines. In vivo testing of the lead molecule in the sulfamide series, in cotreatment with doxorubicin, demonstrated a chemosensitization of CA IX containing tumors. Such CA inhibitors, specifically targeting the tumor-associated isoforms, are candidates for novel treatment strategies against hypoxic tumors overexpressing extracellular CA isozymes.

  DOI：

  10.1021/jm4009532
• 作为产物：
  描述：

  2-硝基咪唑 、 溴乙酸叔丁酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 tert-butyl 2-(2-nitro-1H-imidazol-1-yl)acetate
  参考文献：
  名称：

  含硝基咪唑基团的凡德他尼衍生物作为常氧和缺氧中酪氨酸激酶抑制剂的设计和合成。

  摘要：

  通过在哌啶侧链中引入硝基咪唑基团，设计并制备了 16 种新型表皮生长因子受体 (EGFR)/血管内皮生长因子 (VEGF)-2 抑制剂（硝基咪唑取代的 4-苯胺基喹唑啉衍生物 (16a-p)）以及对vandetanib苯胺部分的修饰。初步生物学试验表明，与凡德他尼相比，部分靶标化合物在缺氧条件下表现出优异的EGFR抑制活性和抗A549/H446细胞增殖活性。同时，上述几种化合物在抑制 VEGF 基因表达方面表现出比凡德他尼更好的生物活性。由于具有优异的IC50值（1.64 μmol/L），在0.5 μM浓度下，16f对A549和H446细胞的抑制率分别为62.01%和59.86%。

  DOI：

  10.3390/molecules21121693

文献信息

• CANCER TARGETING USING CARBONIC ANHYDRASE ISOFORM IX INHIBITORS
  申请人：Lambin Philippe

  公开号：US20130274305A1

  公开（公告）日：2013-10-17

  The present invention concerns novel carbonic anhydrase IX inhibitors comprising a nitroimidazole moiety and their use in therapy of hypoxic conditions, in particular cancer treatment, especially chemotherapy and radiotherapy. The compounds of the invention have an increased specificity for the carbonic anhydrase IX enzyme compared to the art. The present invention relates to novel nitroimidazole derivates represented by formula (1).

  本发明涉及一种新型碳酸酐酶IX抑制剂，其中包括亚硝基咪唑基团，并且其在治疗低氧条件，特别是癌症治疗，尤其是化疗和放疗方面的应用。该发明的化合物与现有技术相比具有更高的碳酸酐酶IX酶的特异性。本发明涉及由式（1）表示的新型亚硝基咪唑衍生物。
• Cancer targeting using carbonic anhydrase isoform IX inhibitors
  申请人：Lambin Philippe

  公开号：US08980932B2

  公开（公告）日：2015-03-17

  The present invention concerns novel carbonic anhydrase IX inhibitors comprising a nitroimidazole moiety and their use in therapy of hypoxic conditions, in particular cancer treatment, especially chemotherapy and radiotherapy. The compounds of the invention have an increased specificity for the carbonic anhydrase IX enzyme compared to the art. The present invention relates to novel nitroimidazole derivates represented by formula (1).

  本发明涉及一种新型的碳酸酐酶IX抑制剂，包括亚硝基咪唑基团，并且可以用于治疗缺氧症状，特别是癌症治疗，尤其是化疗和放疗。本发明的化合物相对于现有技术具有较高的碳酸酐酶IX酶特异性。本发明涉及由式（1）表示的新型亚硝基咪唑衍生物。
• Synthesis of new 18F-radiolabeled silicon-based nitroimidazole compounds
  作者：Yoann Joyard、Rabah Azzouz、Laurent Bischoff、Cyril Papamicaël、Daniel Labar、Anne Bol、Vanessa Bol、Pierre Vera、Vincent Grégoire、Vincent Levacher、Pierre Bohn

  DOI：10.1016/j.bmc.2013.04.029

  日期：2013.7

  The syntheses of new nitroimidazole compounds using silicon-[F-18]fluorine chemistry for the potential detection of tumor hypoxia are described. [F-18]silicon-based compounds were synthesized by coupling 2-nitroimidazole with silyldinaphtyl or silylphenyldi-tert-butyl groups and labeled by fluorolysis or isotopic exchange. Dinaphtyl compounds (6, 10) were labeled in 56-71% yield with a specific activity of 45 GBq/mu mol, however these compounds ([F-18]7 and [F-18]11) were not stable in plasma. Phenyldi-tert-butyl compounds were labeled in 70% yield with a specific activity of 3 GBq/mu mol by isotopic exchange, or in 81% yield by fluorolysis of siloxanes with a specific activity of 45 GBq/mu mol. The labeled compound [F-18]18 was stable in plasma and excreted by the liver and kidneys in vivo. In conclusion, the fluorosilylphenyldi-tert-butyl (SiFA) group is more stable in plasma than fluorosilyldiphenyl moiety. Thus, compound [F-18]18 is suitable for further in vivo assessments. (C) 2013 Elsevier Ltd. All rights reserved.
• [EN] CANCER TARGETING USING CARBONIC ANHYDRASE ISOFORM IX INHIBITORS<br/>[FR] CIBLAGE DE CANCER UTILISANT DES INHIBITEURS D'ISOFORME IX D'ANHYDRASE CARBONIQUE
  申请人：STICHTING MAASTRICHT RADIATION ONCOLOGY MAASTRO CLINIC

  公开号：WO2012087115A8

  公开（公告）日：2013-09-19
• WEBB, PAUL;THREADGILL, MICHAEL D., J. LABELL. COMPOUNDS AND RADIOPHARM., 28,(1990) N, C. 265-271
  作者：WEBB, PAUL、THREADGILL, MICHAEL D.

  DOI：——

  日期：——