2-(2-硝基-1H-咪唑-1-基)乙胺盐酸盐 | 116989-51-6

• 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
• 中文名称: 2-(2-硝基-1H-咪唑-1-基)乙胺盐酸盐
• 英文名称: 2-(2-nitro-1H-imidazolyl)ethylamine hydrochloride
• 英文别名: 2-(2-Nitro-1h-imidazol-1-yl)ethanamine hydrochloride；2-(2-nitroimidazol-1-yl)ethanamine;hydrochloride
• CAS: 116989-51-6
• 化学式: C₅H₈N₄O₂*ClH
• 分子量: 192.605
• InChiKey: UNLRFFXZTJXMPL-UHFFFAOYSA-N

物化性质

• 熔点：
  171 °C(Solv: methanol (67-56-1); ethyl ether (60-29-7))

计算性质

• 辛醇/水分配系数(LogP)：
  0.17
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  89.7
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-(2-硝基-1H-咪唑-1-基)乙胺盐酸盐 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  Development of 68Ga-labeled multivalent nitroimidazole derivatives for hypoxia imaging

  摘要：

  Radiolabeled nitroimidazole (NI) derivatives have been extensively studied for imaging hypoxia. To increase the hypoxic tissue uptake, we developed Ga-68-labeled agents based on mono-, bis-, and trisnitroimidazole conjugates with the chelating agent 1,4,7-triazacyclononane-1,4,7-tris[methyl(2-carboxyethyl)phosphinic acid] (TRAP). All the three agents showed high radiolabeling yields (> 96%) and were found to be stable up to 4 h in prepared medium at room temperature and in human serum at 37 degrees C. The trivalent agent showed a significant increase in hypoxic to normoxic uptake ratio (p < 0.005) according to the in vitro cell uptake experiments. Immunohistochemical analysis confirmed the presence of hypoxia in xenografted CT26 tumor tissue. The trivalent derivative (Ga-68-3: 0.17 +/- 0.04, Ga-68-4: 0.33 +/- 0.04, Ga-68-5: 0.45 +/- 0.09, and Ga-68-6: 0.47 +/- 0.05% ID/g) showed the highest uptake by tumor cells according to the biodistribution studies in CT-26 xenografted mice. All the nitroimidazole derivatives showed significantly higher uptake by tumor cells than the control agent (p < 0.05) at 1 h post-injection. The trivalent derivative (Ga-68-3: 0.10 +/- 0.06; Ga-68-4: 0.20 +/- 0.06; Ga-68-5: 0.33 +/- 0.08; Ga-68-6: 0.59 +/- 0.09) also showed the highest standard uptake value for tumor cells at 1 h post-injection in animal PET studies using CT-26 xenografted mice. In conclusion, we successfully synthesized multivalent Ga-68-labeled NI derivatives for imaging hypoxia. Among them, the trivalent agent showed the highest tumor uptake in biodistribution and animal PET studies. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.024
• 作为产物：
  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

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。
• Neopentyl Glycol as a Scaffold to Provide Radiohalogenated Theranostic Pairs of High <i>In Vivo</i> Stability
  作者：Hiroyuki Suzuki、Yuta Kaizuka、Maho Tatsuta、Hiroshi Tanaka、Nana Washiya、Yoshifumi Shirakami、Kazuhiro Ooe、Atsushi Toyoshima、Tadashi Watabe、Takahiro Teramoto、Ichiro Sasaki、Shigeki Watanabe、Noriko S. Ishioka、Jun Hatazawa、Tomoya Uehara、Yasushi Arano

  DOI：10.1021/acs.jmedchem.1c01147

  日期：2021.11.11

  vivo deiodination. 211At-labeled neopentyl glycol also remained stable against both nucleophilic substitution and CYP-mediated metabolism. 211At-labeled neopentyl glycol showed the biodistribution profiles similar to those of its radioiodinated counterpart in contrast to the 125I/211At-labeled benzoate pair. The urine analyses confirmed that 211At-labeled neopentyl glycol was excreted in the urine as a

  2,2-二羟甲基-3-[ 18 F]氟丙基-2-硝基咪唑（[ 18 F]DiFA）的高体内稳定性促使我们评估新戊基作为支架以制备具有放射性碘和砹的放射治疗系统。合成了三种具有一个、两个或没有羟基的 DiFA 类似物。虽然所有125 I 标记的化合物对亲核取代保持稳定，但只有125 I 标记的新戊二醇对细胞色素 P450 (CYP) 介导的代谢保持稳定，并显示出对体内脱碘的高稳定性。211 At 标记的新戊二醇对亲核取代和 CYP 介导的代谢也保持稳定。与125 I/ 211 At 标记的苯甲酸酯对相比， 211 At 标记的新戊二醇显示出与其放射性碘化对应物相似的生物分布曲线。尿液分析证实，211 At 标记的新戊二醇作为葡萄糖苷酸结合物从尿液中排出，不含游离的 [ 211 At]At –。这些发现表明，新戊二醇将构成一个有前途的支架，用于制备含有放射性碘和211 At 的放射治疗系统。
• DIAGNOSTIC AGENT FOR INFECTIOUS DISEASES
  申请人：Sakurai Kazuhisa

  公开号：US20120219500A1

  公开（公告）日：2012-08-30

  A diagnostic agent for infectious diseases which is capable of distinguishing among different kinds of bacterial species and which allows simple and non-invasive measurement and/or imaging in a short period of time is provided; and a screening method for a therapeutic agent for infectious diseases caused by microorganisms are provided. A diagnostic agent for infectious diseases caused by nitroimidazole susceptible microorganisms, containing an imidazole derivative or a fused imidazole derivative having at least one nitro group on an imidazole ring, or a labeled form thereof as an active ingredient is provided.

  提供了一种针对传染病的诊断试剂，能够区分不同种类的细菌，并允许在短时间内进行简单、非侵入性的测量和/或成像；同时提供了一种筛选治疗由微生物引起的传染病的方法。提供了一种针对对硝基咪唑敏感微生物引起的传染病的诊断试剂，其包含一种咪唑衍生物或至少在咪唑环上具有一个硝基基团的融合咪唑衍生物，或其标记形式作为活性成分。
• Synthesis and Evaluation of Technetium-99m-Labeled Bioreductive Pharmacophores Conjugated with Amino Acids and Peptides for Tumor Imaging
  作者：Rinku Baishya、Dipak K. Nayak、Sanmoy Karmakar、Sankha Chattopadhyay、Satbir S. Sachdeva、Bharat R. Sarkar、Shantanu Ganguly、Mita C. Debnath

  DOI：10.1111/cbdd.12437

  日期：2015.4

  imaging agents to target tumor has become a major trend in nuclear medicine. With the aim to develop new potential 99mTc‐radiopharmaceuticals for targeting tumor, we have synthesized 5‐nitroimidazolyl amino acids and RGD‐coupled 2‐nitroimidazoles. Technetium‐99m radiolabeling with high radiochemical purity (>90%) was achieved for all the compounds. The radiolabeled complexes exhibited substantial in vitro

  靶向肿瘤的分子显像剂的开发已成为核医学的主要趋势。为了开发新的潜在99m Tc放射性药物靶向肿瘤，我们合成了5-硝基咪唑基氨基酸和RGD偶联的2-硝基咪唑。所有化合物均实现了具有高放射化学纯度（> 90％）的99m放射性标记。放射性标记的复合物在盐水，血清和组氨酸溶液（10 -2 m）中表现出显着的体外稳定性。EAC和B16F10细胞系中的细胞结合研究也显示出快速且相对较高的细胞内在化。在所有研究的化合物，的结合99米TC（CO）3 - 5 到B16F10细胞通过适度的竞争肽C [RGDfV]抑制，表明所述放射性配体的特异性朝向α v β 3受体。但是，当99m Tc标记的复合物与上述细胞的结合受到过量竞争肽的挑战时，未观察到结合放射性配体的显着位移。荧光显微镜研究提供的5（6）细胞内定位-羧基标记的2-硝基咪唑-RGD肽在的直接证据α v β 3阳性B16F10小鼠黑色素瘤细胞系。的配位
• High selectivity imaging of nitroreductase using a near-infrared fluorescence probe in hypoxic tumor
  作者：Kehua Xu、Feng Wang、Xiaohong Pan、Renpu Liu、Jing Ma、Fanpeng Kong、Bo Tang

  DOI：10.1039/c3cc38980d

  日期：——

  A highly selective and sensitive near-infrared (NIR) fluorescence probe (Cy-NO2) for imaging nitroreductase was developed and was successfully applied to investigating the relationship between epithelial–mesenchymal transitions (EMTs) in tumour progression and intracellular hypoxic level.

  研究人员开发了一种高度选择性和灵敏的近红外（NIR）荧光探针（Cy-NO2），用于成像硝基还原酶，并成功应用于研究肿瘤进展中的上皮-间质转化（EMT）与细胞内低氧水平之间的关系。