1-(chloromethyl)-2-nitro-1H-imidazole | 1569296-82-7

• 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: 1-(chloromethyl)-2-nitro-1H-imidazole
• 英文别名: 1-(chloromethyl)-2-nitroimidazole
• CAS: 1569296-82-7
• 化学式: C₄H₄ClN₃O₂
• 分子量: 161.548
• InChiKey: INKSBMJCUWMIPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  1-(chloromethyl)-2-nitro-1H-imidazole 在 sodium sulfite 作用下， 以 水 、 丙酮 为溶剂， 反应 2.0h， 生成 sodium (2-nitro-1H-imidazol-1-yl)methanesulfonate
  参考文献：
  名称：

  Novel nitroimidazole alkylsulfonamides as hypoxic cell radiosensitisers

  摘要：

  A novel class of nitroimidazole alkylsulfonamides have been prepared and evaluated as hypoxia-selective cytotoxins and radiosensitisers. The sulfonamide side chain markedly influences the physicochemical properties of the analogues: lowering aqueous solubility and raising the electron affinity of the nitroimidazole group. The addition of hydroxyl or basic amine groups increased aqueous solubility, with charged amine groups contributing to increased electron affinity. The analogues covered the range of electron affinity for effective radiosensitisation with one-electron reduction potentials ranging from -503 to -342 mV. Cytotoxicity under normoxia or anoxia against a panel of human tumour cell lines was determined using a proliferation assay. 2-Nitroimidazole sulfonamides displayed significant hypoxia-selective cytotoxicity ( 6 to 64-fold), while 4- and 5-nitroimidazole analogues did not display hypoxia-selective cytotoxicity. All analogues sensitised anoxic HCT-116 human colorectal cells to radiation at non-toxic concentrations. 2-Nitroimidazole analogues provided modest sensitisation due to the relatively low concentrations used while several 5-nitroimidazole analogues provided equivalent sensitisation to misonidazole and etanidazole at similar molar concentrations. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.039
• 作为产物：
  描述：

  2-硝基咪唑 、 溴氯甲烷 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以45%的产率得到1-(chloromethyl)-2-nitro-1H-imidazole
  参考文献：
  名称：

  厌氧菌启发的抗癌纳米囊泡

  摘要：

  厌氧菌，如梭菌和沙门氏菌可以选择性地侵入并在肿瘤低氧区域（THRs）定居，并提供治疗性产品来破坏癌细胞。在本文中，我们提出了一种厌氧菌纳米囊模拟物，它不仅可以在THRs中被激活，而且还可以自身诱导肿瘤缺氧。此外，受厌氧菌氧代谢的启发，我们构建了一种光诱导的低氧反应性模式，以同时促进媒介物的解离和生物还原性前药的激活。体外和体内实验表明，这种厌氧菌激发的纳米囊泡可有效诱导凋亡细胞死亡并显着抑制肿瘤生长。我们的工作为以生物启发和协同方式设计刺激响应性药物递送系统提供了新的策略。

  DOI：

  10.1002/anie.201611783

文献信息

• Next-Generation Hypoxic Cell Radiosensitizers: Nitroimidazole Alkylsulfonamides
  作者：Muriel Bonnet、Cho Rong Hong、Way Wua Wong、Lydia P. Liew、Avik Shome、Jingli Wang、Yongchuan Gu、Ralph J. Stevenson、Wen Qi、Robert F. Anderson、Frederik B. Pruijn、William R. Wilson、Stephen M. F. Jamieson、Kevin O. Hicks、Michael P. Hay

  DOI：10.1021/acs.jmedchem.7b01678

  日期：2018.2.8

  document their cytotoxicity and ability to radiosensitize anoxic tumor cells in vitro. We use a phosphate prodrug approach to increase aqueous solubility and to improve tumor drug delivery. A 2-nitroimidazole and a 5-nitroimidazole analogue demonstrated marked tumor radiosensitization in either ex vivo assays of surviving clonogens or tumor regrowth delay.

  立体定向身体放疗等放疗领域的创新，以及放射免疫肿瘤学的出现，为经典的模拟氧放射增敏剂带来了新的机遇。缺氧肿瘤细胞在放射疗法抗性和免疫应答抑制中的作用继续证明肿瘤缺氧是一种真正的但尚未开发的药物靶标。临床上仅将尼莫拉唑用作放射增敏剂，并且尚无开发中的新的放射增敏剂。在这里，我们目前对新型硝基咪唑烷基磺酰胺类药物进行调查，并记录它们的细胞毒性和在体外对缺氧肿瘤细胞放射增敏的能力。我们使用磷酸盐前药方法来增加水溶性并改善肿瘤药物的递送。
• [EN] PATCH LOADED WITH DUAL-SENSITIVE VESICLES FOR ENHANCED GLUCOSE-RESPONSIVE INSULIN DELIVERY<br/>[FR] PATCH CHARGÉ DE VÉSICULES DOUBLEMENT SENSIBLES DESTINÉ À UNE AMÉLIORATION DE L'APPORT D'INSULINE EN RÉACTION AU GLUCOSE
  申请人：UNIV NORTH CAROLINA STATE

  公开号：WO2018085809A1

  公开（公告）日：2018-05-11

  A composition comprising an amphiphilic polymeric material that is both hydrogen peroxide- and hypoxia-sensitive is described. The composition can further include a glucose-oxidizing enzyme and insulin, a bioactive derivative thereof, and/or another therapeutic agent (e.g., another diabetes treatment agent). The polymeric material can form vesicles that comprise single or multiple layers of the polymeric material that enclose the glucose-oxidizing enzyme and the insulin, bioactive derivative and/or other therapeutic agent. The vesicles can be loaded into microneedles to, for example, prepare microneedle arrays for skin patches. Methods of delivering insulin to a subject using the compositions, vesicles, microneedles, and/or microneedle array skin patches are also described.

  描述了一种包括既对过氧化氢敏感又对缺氧敏感的两性聚合物材料的组合物。该组合物还可以包括葡萄糖氧化酶和胰岛素，其生物活性衍生物和/或其他治疗剂（例如，另一种糖尿病治疗剂）。聚合物材料可以形成包含葡萄糖氧化酶和胰岛素、生物活性衍生物和/或其他治疗剂的单层或多层聚合物材料的囊泡。这些囊泡可以装载到微针中，例如，制备用于皮肤贴片的微针阵列。还描述了使用这些组合物、囊泡、微针和/或微针阵列皮肤贴片向受试者输送胰岛素的方法。
• [EN] NITROIMIDAZOLE COMPOUNDS AND THEIR USE IN CANCER THERAPY<br/>[FR] COMPOSÉS DE NITROIMIDAZOLE ET LEUR UTILISATION EN THÉRAPIE ANTICANCÉREUSE
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2014030142A3

  公开（公告）日：2014-04-17
• Novel nitroimidazole alkylsulfonamides as hypoxic cell radiosensitisers
  作者：Muriel Bonnet、Cho Rong Hong、Yongchuan Gu、Robert F. Anderson、William R. Wilson、Frederik B. Pruijn、Jingli Wang、Kevin O. Hicks、Michael P. Hay

  DOI：10.1016/j.bmc.2014.02.039

  日期：2014.4

  A novel class of nitroimidazole alkylsulfonamides have been prepared and evaluated as hypoxia-selective cytotoxins and radiosensitisers. The sulfonamide side chain markedly influences the physicochemical properties of the analogues: lowering aqueous solubility and raising the electron affinity of the nitroimidazole group. The addition of hydroxyl or basic amine groups increased aqueous solubility, with charged amine groups contributing to increased electron affinity. The analogues covered the range of electron affinity for effective radiosensitisation with one-electron reduction potentials ranging from -503 to -342 mV. Cytotoxicity under normoxia or anoxia against a panel of human tumour cell lines was determined using a proliferation assay. 2-Nitroimidazole sulfonamides displayed significant hypoxia-selective cytotoxicity ( 6 to 64-fold), while 4- and 5-nitroimidazole analogues did not display hypoxia-selective cytotoxicity. All analogues sensitised anoxic HCT-116 human colorectal cells to radiation at non-toxic concentrations. 2-Nitroimidazole analogues provided modest sensitisation due to the relatively low concentrations used while several 5-nitroimidazole analogues provided equivalent sensitisation to misonidazole and etanidazole at similar molar concentrations. (C) 2014 Elsevier Ltd. All rights reserved.
• Anaerobe-Inspired Anticancer Nanovesicles
  作者：Chenggen Qian、Peijian Feng、Jicheng Yu、Yulei Chen、Quanyin Hu、Wujin Sun、Xuanzhong Xiao、Xiuli Hu、Adriano Bellotti、Qun-Dong Shen、Zhen Gu

  DOI：10.1002/anie.201611783

  日期：2017.3.1

  in THRs but also induce hypoxia in tumors by themselves. Moreover, inspired by the oxygen metabolism of anaerobes, we construct a light‐induced hypoxia‐responsive modality to promote dissociation of vehicles and activation of bioreductive prodrugs simultaneously. In vitro and in vivo experiments indicate that this anaerobe‐inspired nanovesicle can efficiently induce apoptotic cell death and significantly

  厌氧菌，如梭菌和沙门氏菌可以选择性地侵入并在肿瘤低氧区域（THRs）定居，并提供治疗性产品来破坏癌细胞。在本文中，我们提出了一种厌氧菌纳米囊模拟物，它不仅可以在THRs中被激活，而且还可以自身诱导肿瘤缺氧。此外，受厌氧菌氧代谢的启发，我们构建了一种光诱导的低氧反应性模式，以同时促进媒介物的解离和生物还原性前药的激活。体外和体内实验表明，这种厌氧菌激发的纳米囊泡可有效诱导凋亡细胞死亡并显着抑制肿瘤生长。我们的工作为以生物启发和协同方式设计刺激响应性药物递送系统提供了新的策略。