1-(4-bromobutyl)-4-nitro-1H-imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-bromobutyl)-4-nitro-1H-imidazole
• 英文别名: 4-nitro-1-(4-bromobutyl)-1H-imidazole；1-(4-bromobutyl)-4-nitroimidazole
• 化学式: C₇H₁₀BrN₃O₂
• 分子量: 248.079
• InChiKey: KOGZSTVKCCNIIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  disodium cis-1,2-dicyano-1,2-ethylenedithiolate 、 1-(4-bromobutyl)-4-nitro-1H-imidazole 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以60%的产率得到2,3-bis((4-(4-nitro-1H-imidazol-1-yl)butyl)thio)maleonitrile
  参考文献：
  名称：

  Synthesis, characterization, photochemical properties and cytotoxicity of the novel porphyrazine functionalized with nitroimidazolylbutylsulfanyl groups

  摘要：

  A novel porphyrazine analog possessing nitroimidazolylbutylsulfanyl groups was synthesized and characterized using UV-Vis, IR, MS MALDI and various NMR techniques. In addition, a computational model following the Density Functional Theory method (DFT) was applied to analyze the FT IR spectrum. Potential photosensitizing activity of the novel porphyrazine was evaluated by measuring its ability to generate singlet oxygen (Phi(Delta)), which was found to reach the value of 0.045 in DMF, and 0.035 in DMSO. A lower value of singlet oxygen generation in DMSO may result from the increased tendency to aggregate, which was studied in the UV-Vis and it was found to be stronger in DMSO than in DMF solutions. The investigation indicated no release of nitric oxide (NO) from porphyrazine functionalized with nitroimidazolylbutylsulfanyl groups. In vitro studies of the new compound were carried out to investigate photosensitizer-induced photocytotoxicity on two prostate human cancer cell lines, LNCaP, PC3, and one melanoma derived cell line, MeWo. (c) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.inoche.2013.01.001
• 作为产物：
  描述：

  1,4-二溴丁烷 、 4-硝基-3H-咪唑 在 四丁基溴化铵 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 7.0h， 生成 1-(4-bromobutyl)-4-nitro-1H-imidazole
  参考文献：
  名称：

  发现具有体外和体内抗癌活性的新型 Celastrol-咪唑衍生物

  摘要：

  为了发现具有增强的 Hsp90–Cdc37 抑制作用的 celastrol (CEL) 衍生物，C-20-COOH 被引入了各种取代的咪唑，这可能会通过亲核攻击影响 CEL 的迈克尔加成。从 28 种新的目标化合物中选出最有效的化合物9，它显示出比 CEL 更高的抗增殖、共价结合能力和 Hsp90–Cdc37 抑制作用。然后，研究了9与Hsp90和Cdc37的结合位点和对接方式。此外，在过表达 Hsp90 和/或 Cdc37 的 A549 细胞中， 9的活性急剧下降甚至消失，表明该活性与其与 Hsp90 和 Cdc37 的组合有关。此外，9体内比 CEL 能 更 有效 地 诱导 细胞 凋亡 和 抑制 肿瘤 生长. 本研究首次发现与CEL的C-20连接的咪唑类可能会影响其迈克尔加成，这将为CEL甚至其他迈克尔受体作为抗肿瘤药物的发展提供支持。

  DOI：

  10.1021/acs.jmedchem.1c01293

文献信息

• 一种含硝基咪唑的多硼苯丙氨酸类化合物及其制备方法和应用
  申请人：中国药科大学

  公开号：CN109942608A

  公开（公告）日：2019-06-28

  本发明公开了一种如通式(I)所示的含硝基咪唑的多硼苯丙氨酸类化合物或其药学上可接受的盐，及其制备方法和应用。本发明所述化合物可通过取代、加成、硝化及脱保护反应制得，具有以下优点：成本低、易于制备、可提供高含量的硼并且对肿瘤细胞具有很高的亲和力、对肿瘤乏氧区域有特异性的响应、稳定性好、生物毒性低。本发明所述含硼化合物的药物组合物，在BNCT中具有较好的应用前景。
• Bu3SnH mediated oxidative radical cyclisation onto imidazoles and pyrroles
  作者：Fawaz Aldabbagh、W.Russell Bowman、Emma Mann、Alexandra M.Z. Slawin

  DOI：10.1016/s0040-4020(99)00419-6

  日期：1999.6

  A new protocol using radical cyclisation has been developed for the synthesis of [1,2-c]-fused imidazoles and [1,2-a]-fused pyrroles. The intermediate nucleophilic N-alkyl radicals, generated using Bu3SnH from N-(omega-bromoalkyl) or N-[omega-(phenylselanyl)alkyl] imidazoles and pyrroles, undergo regioselective radical cyclisation onto the azole rings followed by oxidative re-aromatisation, (C) 1999 Elsevier Science Ltd. Ail rights reserved.
• Discovery of novel hypoxia-activated, nitroimidazole constructed multi-target kinase inhibitors on the basis of AZD9291 for the treatment of human lung cancer
  作者：Tingting Jia、Ruoyang Miao、Jiankang Zhang、Huajian Zhu、Chong Zhang、Linghui Zeng、Yanmei Zhao、Weiyan Cheng、Jiaan Shao

  DOI：10.1016/j.bmc.2023.117384

  日期：2023.8
• Synthesis, characterization, photochemical properties and cytotoxicity of the novel porphyrazine functionalized with nitroimidazolylbutylsulfanyl groups
  作者：Sebastian Lijewski、Jaroslaw Piskorz、Malgorzata Kucinska、Marcin Wierzchowski、Katarzyna Czerniak、Hanna Billert、Marek Murias、Jadwiga Mielcarek、Tomasz Goslinski

  DOI：10.1016/j.inoche.2013.01.001

  日期：2013.3

  A novel porphyrazine analog possessing nitroimidazolylbutylsulfanyl groups was synthesized and characterized using UV-Vis, IR, MS MALDI and various NMR techniques. In addition, a computational model following the Density Functional Theory method (DFT) was applied to analyze the FT IR spectrum. Potential photosensitizing activity of the novel porphyrazine was evaluated by measuring its ability to generate singlet oxygen (Phi(Delta)), which was found to reach the value of 0.045 in DMF, and 0.035 in DMSO. A lower value of singlet oxygen generation in DMSO may result from the increased tendency to aggregate, which was studied in the UV-Vis and it was found to be stronger in DMSO than in DMF solutions. The investigation indicated no release of nitric oxide (NO) from porphyrazine functionalized with nitroimidazolylbutylsulfanyl groups. In vitro studies of the new compound were carried out to investigate photosensitizer-induced photocytotoxicity on two prostate human cancer cell lines, LNCaP, PC3, and one melanoma derived cell line, MeWo. (c) 2013 Elsevier B.V. All rights reserved.
• Discovery of Novel Celastrol–Imidazole Derivatives with Anticancer Activity <i>In Vitro</i> and <i>In Vivo</i>
  作者：Na Li、Manyi Xu、Lulu Zhang、Zhichao Lei、Cheng Chen、Tianyuan Zhang、Li Chen、Jianbo Sun

  DOI：10.1021/acs.jmedchem.1c01293

  日期：2022.3.24

  To discover celastrol (CEL) derivatives with enhanced Hsp90–Cdc37 inhibition, C-20-COOH was introduced with various substituted imidazoles, which might affect the Michael addition of CEL by nucleophilic attack. The most potent compound 9, which showed higher antiproliferation, covalent-binding ability, and Hsp90–Cdc37 inhibition than CEL, was selected from 28 new target compounds. Then, the binding

  为了发现具有增强的 Hsp90–Cdc37 抑制作用的 celastrol (CEL) 衍生物，C-20-COOH 被引入了各种取代的咪唑，这可能会通过亲核攻击影响 CEL 的迈克尔加成。从 28 种新的目标化合物中选出最有效的化合物9，它显示出比 CEL 更高的抗增殖、共价结合能力和 Hsp90–Cdc37 抑制作用。然后，研究了9与Hsp90和Cdc37的结合位点和对接方式。此外，在过表达 Hsp90 和/或 Cdc37 的 A549 细胞中， 9的活性急剧下降甚至消失，表明该活性与其与 Hsp90 和 Cdc37 的组合有关。此外，9体内比 CEL 能 更 有效 地 诱导 细胞 凋亡 和 抑制 肿瘤 生长. 本研究首次发现与CEL的C-20连接的咪唑类可能会影响其迈克尔加成，这将为CEL甚至其他迈克尔受体作为抗肿瘤药物的发展提供支持。