3-(2-nitro-1H-imidazolyl)propionic acid | 97762-32-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2-nitro-1H-imidazolyl)propionic acid
• 英文别名: 4-(2-nitro-1H-imidazolyl)propanoic acid；3-(2-nitro-1-imidazolyl)propionic acid；3-(2-nitroimidazol-1-yl)propionic acid；3-(2-Nitro-1h-imidazol-1-yl)propanoic acid；3-(2-nitroimidazol-1-yl)propanoic acid
• CAS: 97762-32-8
• 化学式: C₆H₇N₃O₄
• 分子量: 185.139
• InChiKey: REMHZMMYLASIBY-UHFFFAOYSA-N

物化性质

• 沸点：
  480.7±47.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-nitro-1H-imidazolyl)propionic acid 在 盐酸 、 dimethyl sulfide borane 作用下， 生成 3-(2-硝基咪唑-1-基)丙-1-醇
  参考文献：
  名称：

  缺氧选择性抗肿瘤药。10.双（硝基咪唑）和相关的双（硝基杂环）：开发在缺氧条件下具有较高代谢活化速率和改善的水溶性的衍生物。

  摘要：

  先前描述的化合物N- [2-（2-甲基-5-硝基咪唑-1H-基）乙基] -4-（2-硝基咪唑-1H-基）丁酰胺的一系列类似物（4），一种新型的低氧细胞已经制备了细胞毒素和放射增敏剂，并对其体外的低氧选择性细胞毒性和低氧细胞放射增敏进行了评估。设计新的衍生物以克服4的低水溶性和在低氧条件下的缓慢杀灭动力学。硝基杂环单元对溶解度有显着影响，其中3-硝基三唑的溶解度是相应的2-硝基咪唑的约6倍。具有一系列中性接头链（多羟基，链烷磺酰胺和双酰胺）的类似物仅显示出略微改善的溶解度，无法完全评估。然而，一系列带有阳离子胺连接基的类似物具有足够的水溶性（最高280 mM）。不能通过直接还原前体酰胺（例如4）来制备胺类似物，并且最方便地通过适当的叠氮化物和醛组分的氮杂-维蒂希缩合合成胺类似物。胺连接的化合物比4具有更高的细胞毒性，对称的双（2-硝基咪唑）衍生物（13和14）的效力最高可达9倍。他们表现出的

  DOI：

  10.1021/jm00011a013
• 作为产物：
  描述：

  methyl 3-(2-nitro-1H-imidazolyl)propionate 在 盐酸 作用下， 反应 4.0h， 以96%的产率得到3-(2-nitro-1H-imidazolyl)propionic acid
  参考文献：
  名称：

  Hay; Wilson; Moselen, Journal of Medicinal Chemistry, 1994, vol. 37, # 3, p. 381 - 391

  摘要：

  DOI：

文献信息

• PRODRUG USING NITROIMIDAZOLE
  申请人：UNIVERSITY OF TSUKUBA

  公开号：US20140378673A1

  公开（公告）日：2014-12-25

  Provided is a prodrug of 2-nitro-1-imidazolepropionic acid and a therapeutically active organic compound having on the molecule an amino group, a cyclic amino group or a hydroxyl group, particularly a prodrug in which the therapeutically active organic compound is selected from among antitumor agents. The prodrug cleaves specifically under hypoxic conditions in vivo to exhibit the inherent therapeutic activity.

  提供的是2-硝基-1-咪唑丙酸的前药和在分子上具有氨基、环氨基或羟基的治疗活性有机化合物，特别是一种前药，其中治疗活性有机化合物从抗肿瘤药物中选择。该前药在体内特定低氧条件下特异性解离，展现固有的治疗活性。
• Nitroimidazole conjugates of bis(thiosemicarbazonato)64Cu(II) – Potential combination agents for the PET imaging of hypoxia
  作者：Paul D. Bonnitcha、Simon R. Bayly、Mark B.M. Theobald、Helen M. Betts、Jason S. Lewis、Jonathan R. Dilworth

  DOI：10.1016/j.jinorgbio.2009.10.009

  日期：2010.2

  Combination agents comprising two different pharmacophores with the same biological target have the potential to show additive or synergistic activity. Bis(thiosemicarbazonato)copper(II) complexes (e.g. Cu-64-ATSM) and nitroimidazoles (e.g. F-18-MISO) are classes of tracer used for the delineation of tumor hypoxia by positron emission tomography (PET). Three nitroimidazole-bis(thiosemicarbazonato)copper(II) conjugates were produced in order to investigate their potential as combination hypoxia imaging agents. Two were derived from the known bifunctional bis(thiosemicarbazone) H(2)ATSM/A and the third from the new precursor diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosemicarbazone) - H(2)ATSM/en. Oxygen-dependent uptake studies were performed using the Cu-64 radiolabelled complexes in EMT6 carcinoma cells. All the complexes displayed appreciable hypoxia selectivity, with the nitroimidazole conjugates displaying greater selectivity than a simple propyl derivative used as a control. Participation of the nitroimidazole group in the trapping mechanism is indicated by the increased hypoxic uptake of the 2- vs. the 4-substituted Cu-64-ATSM/A derivatives. The 2-nitroimidazole derivative of Cu-64-ATSM/en demonstrated superior hypoxia selectivity to Cu-64-ATSM over the range of oxygen concentrations tested. Biodistribution of the radiolabelled 2-nitroimidazole conjugates was carried out in EMT6 tumor-bearing mice. The complexes showed significantly different uptake trends in comparison to each other and previously studied Cu-ATSM derivatives. Uptake of the Cu-ATSM/en conjugate in non-target organs was considerably lower than for derivatives based on Cu-ATSM/A. (C) 2009 Elsevier Inc. All rights reserved.
• Metal complexes as radiosensitizers: Cobalt(II), copper(II), rhodium(II) and platinum(II) complexes of 3-(1-imidazoyl)propionic acid and some nitro-substituted derivatives, and the crystal structure and radiosensitizer activity of [CuL2(H2O)]2 · 2H2O, where LH = 3-[1-(4-nitroimidazoyl)]propionic acid
  作者：David M.L. Goodgame、Christopher J. Page、David J. Williams、Ian J. Stratford

  DOI：10.1016/s0277-5387(00)83571-8

  日期：1992.1

  The preparations are reported of 3-[1-(4-nitroimidazoyl)]propionic acid, 3-[1-(2-methyl-4-nitroimidazoyl)]propionic acid and 3-[1-(2-nitroimidazoyl)]propionic acid, and also of some cobalt(II), copper(II), rhodium(II) and platinum(II) complexes with these ligands or with 3-[1-imidazoyl]propionic acid. The complexes were characterized by spectroscopic methods, and the compound [CuL2(H2O)]2.2H2O, where LH = 3-[1-(4-nitroimidazoyl)]propionic acid, was shown by X-ray diffraction to be dinuclear with each of the organic ligands bonded to two copper(II) ions via the carboxylate groups. Radiosensitization studies on [CuL2(H2O)]2.2H2O using hypoxic Chinese hamster V79 cells gave enhancement ratios similar to those for misonidazole, and significantly greater than those for typical, uncomplexed 4-nitroimidazoles.
• Hay Michael P., Wilson William R., Moselen John W., Palmer Brian D., Denn+, J. Med. Chem, 37 (1994) N 3, S 381-391
  作者：Hay Michael P., Wilson William R., Moselen John W., Palmer Brian D., Denn+

  DOI：——

  日期：——
• US9655975B2
  申请人：——

  公开号：US9655975B2

  公开（公告）日：2017-05-23