tert-butyl (2-(2-nitro-1H-imidazol-1-yl)ethyl)carbamate | 1300727-12-1

• 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: tert-butyl (2-(2-nitro-1H-imidazol-1-yl)ethyl)carbamate
• 英文别名: tert-butyl N-[2-(2-nitroimidazol-1-yl)ethyl]carbamate
• CAS: 1300727-12-1
• 化学式: C₁₀H₁₆N₄O₄
• 分子量: 256.261
• InChiKey: BXPOWKOMCCUXTQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  102
• 氢给体数：
  1
• 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)ethyl)carbamate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以84%的产率得到2-(2-硝基-1H-咪唑-1-基)乙胺盐酸盐
  参考文献：
  名称：

  Synthesis and Characterization of Nitroimidazole Derivatives for ⁶⁸Ga-Labeling and Testing in Tumor Xenografted Mice

  摘要：

  Radiolabeled nitroimidazole (NI) derivatives have been used for imaging hypoxic tissues. We synthesized NI derivatives conjugated with bifunctional chelating agents such as 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and isothiocyanatobenzyl-NOTA (SCN-NOTA) via ethyleneamine bridge by formation of amide and thiourea bond, respectively. We proved that amide oxygen of Ga-NOTA-NI contributes to the formation of metal complex by X-ray crystallography. We labeled them with Ga-68 and found that both Ga-68-NOTA-NI and Ga-68- SCN-NOTA-NI were labeled in high efficiency (> 96%) and were stable at room temperature in the prepared medium and at 37 degrees C in human serum. In vitro cell uptake experiments using CHO and CT-26 cell lines showed significantly increased uptakes of both of the agents in hypoxic condition. Biodistribution study in CT-26 xenografted mice showed increasing tumor to muscle ratios. Ga-68-NOTA-NI showed lower intestine uptake than Ga-68-NOTA-SCN-NI due to hydrophilicity. Also, Ga-68-NOTA-NI showed higher tumor uptake than Ga-68-NOTA-SCN-NI in an animal PET study. In conclusion, we successfully developed Ga-68 labeled NI derivatives for hypoxic tissue imaging.

  DOI：

  10.1021/jm100545a
• 作为产物：
  描述：

  2-硝基咪唑 、 N-Boc-溴乙胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 tert-butyl (2-(2-nitro-1H-imidazol-1-yl)ethyl)carbamate
  参考文献：
  名称：

  在活细胞中使用 18F 预靶向 IEDDA “点击”化学检测体外缺氧

  摘要：

  我们举例说明了一种使用放射性生物正交逆电子需求 Diels-Alder (IEDDA) “点击”化学来检测活细胞缺氧的预靶向方法。我们的新型18 F-四嗪探针 ([ 18 F]FB-Tz) 和基于 2-硝基咪唑的 TCO 靶向分子 ( 8 )在缺氧细胞中显示出具有统计学意义的 ( P < 0.0001) 摄取（每毫克约90% ID）与.含氧量正常的细胞（<10 %ID/mg）在 [ 18的 60 分钟孵育中F]FB-Tz。这是 IEDDA “click” 的细胞内靶向小分子首次与活细胞中的放射性报告分子结合使用，并且可能是一种有用的工具，对各种应用具有深远的适用性。

  DOI：

  10.1039/d1ra02482e

文献信息

• Synthesis and Stability Evaluation of New HYNIC Derivatives as Ligands for Technetium-99m
  作者：Yoann Joyard、Laurent Bischoff、Vincent Levacher、Cyril Papamicael、Pierre Vera、Pierre Bohn

  DOI：10.2174/15701786113106660087

  日期：2014.2

  An efficient synthetic route to prepare two new HYNIC derivatives with a 2-nitroimidazole moiety designed for tumor hypoxia imaging is described. During the course of the synthesis, the optimization of N-alkylation reaction of 2- nitroimidazole with propargyl bromide is reported to favor the formation of the terminal alkyne versus allene. Thereafter, the two ligands were used with tricine/EDDA to complex 99mTc. However, decomposition of these ligands was observed and we suggest a reasonable explanation based on LC-MS analysis.

  描述了一种高效的合成路线，用于制备两种新型HYNIC衍生物，它们含有2-硝基咪唑结构，设计用于肿瘤乏氧显像。在合成过程中，报道了对2-硝基咪唑与丙炔基溴的N-烷基化反应的优化，这有利于形成末端炔烃而非丙二烯。随后，这两种配体与tricine/EDDA一起用于络合99mTc。然而，观察到了这些配体的分解现象，我们基于LC-MS分析给出了一个合理的解释。
• Design, Synthesis and Anticancer Evaluation of Nitroimidazole Radiosensitisers
  作者：Lydia P. Liew、Avik Shome、Way W. Wong、Cho R. Hong、Kevin O. Hicks、Stephen M. F. Jamieson、Michael P. Hay

  DOI：10.3390/molecules28114457

  日期：——

  The role of hypoxic tumour cells in resistance to radiotherapy, and in suppression of immune response, continues to endorse tumour hypoxia as a bona fide, yet largely untapped, drug target. Radiotherapy innovations such as stereotactic body radiotherapy herald new opportunities for classical oxygen-mimetic radiosensitisers. Only nimorazole is used clinically as a radiosensitiser, and there is a dearth of new radiosensitisers in development. In this report, we augment previous work to present new nitroimidazole alkylsulfonamides and we document their cytotoxicity and ability to radiosensitise anoxic tumour cells in vitro. We compare radiosensitisation with etanidazole and earlier nitroimidazole sulfonamide analogues and we identify 2-nitroimidazole and 5-nitroimidazole analogues with marked tumour radiosensitisation in ex vivo assays of surviving clonogens and with in vivo tumour growth inhibition.

  缺氧肿瘤细胞在抗放疗和抑制免疫反应方面的作用，继续证明肿瘤缺氧是一个真正的、但在很大程度上尚未开发的药物靶点。立体定向体放疗等放疗创新为经典的仿氧放射增敏剂带来了新的机遇。目前临床上只有尼莫拉唑被用作放射增敏剂，而正在开发的新型放射增敏剂却十分匮乏。在本报告中，我们对之前的工作进行了补充，提出了新的硝基咪唑烷基磺酰胺类药物，并记录了它们的细胞毒性和体外使缺氧肿瘤细胞放射增敏的能力。我们比较了依他尼达唑和早期硝基咪唑磺酰胺类似物的放射增敏作用，并确定了 2-硝基咪唑和 5-硝基咪唑类似物，它们在存活克隆体的体内外试验中具有明显的肿瘤放射增敏作用，并能抑制体内肿瘤生长。
• Oxygen-release microspheres capable of releasing oxygen in response to environmental oxygen level to improve stem cell survival and tissue regeneration in ischemic hindlimbs
  作者：Ya Guan、Ning Gao、Hong Niu、Yu Dang、Jianjun Guan

  DOI：10.1016/j.jconrel.2021.01.034

  日期：2021.3
• Hypoxia-Targeting Carbonic Anhydrase IX Inhibitors by a New Series of Nitroimidazole-Sulfonamides/Sulfamides/Sulfamates
  作者：Marouan Rami、Ludwig Dubois、Nanda-Kumar Parvathaneni、Vincenzo Alterio、Simon J. A. van Kuijk、Simona Maria Monti、Philippe Lambin、Giuseppina De Simone、Claudiu T. Supuran、Jean-Yves Winum

  DOI：10.1021/jm4009532

  日期：2013.11.14

  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.
• Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers
  作者：Lathika Hoigebazar、Jae Min Jeong、Mee Kyung Hong、Young Ju Kim、Ji Youn Lee、Dinesh Shetty、Yun-Sang Lee、Dong Soo Lee、June-Key Chung、Myung Chul Lee

  DOI：10.1016/j.bmc.2011.02.041

  日期：2011.4

  The imaging of hypoxia is important for therapeutic decision making in various diseases. Ga-68 is an important radionuclide for positron emission tomography (PET), and its usage is increasing, due to the development of the Ge-68/Ga-68-generator. In the present study, the authors synthesized two nitroimidazole derivatives by conjugating nitroimidazole and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an amide bond (4) and a thiourea bond (5). Both derivatives were labeled with Ga-68 with high labeling efficiency and were stable after labeling. The low partition coefficients (log P) of Ga-68-4 (-4.6) and Ga-68-5 (-4.5) demonstrated the hydrophilic natures of the derivatives, and both showed higher uptake in cancer cell lines cultured under hypoxic condition than under normoxic condition. However, Ga-68-5 showed higher liver uptake than Ga-68-4 in a biodistribution study due to higher lipophilicity. In an animal PET study, Ga-68-4 showed higher standard uptake values (SUV) in tumors than Ga-68-5 in mice xenografted with CT-26 mouse colon cancer cells. (C) 2011 Elsevier Ltd. All rights reserved.