5-(溴甲基)-1-甲基-4-硝基-1H-咪唑 | 1017279-02-5

• 物质功能分类: 化学农药原药 - 杀虫剂 - 氨基甲酸酯杀虫剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(溴甲基)-1-甲基-4-硝基-1H-咪唑
• 英文名称: 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole
• 英文别名: 5-(bromomethyl)-1-methyl-4-nitroimidazole
• CAS: 1017279-02-5
• 化学式: C₅H₆BrN₃O₂
• 分子量: 220.026
• InChiKey: HASKXMPCTDGSDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 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：

  (-)-antofine 、 5-(溴甲基)-1-甲基-4-硝基-1H-咪唑 以 氯仿 为溶剂， 反应 20.0h， 以52%的产率得到(13aR)-2,3,6-trimethoxy-10-((1-methyl-4-nitro-1H-imidazol-5-yl)methyl)-10,11,12,13,13a,14-hexahydro-9H-dibenzo[f,h]pyrrolo[1,2-b]isoquinolin-10-ium bromide
  参考文献：
  名称：

  Antofine 和 Tylophorine 前药作为缺氧靶向抗癌药物的设计、合成和体外生物学评价

  摘要：

  菲并吲哚里西啶，例如安托芬和泰洛佛林，是从不同种类的萝藦科植物中分离出来的一类天然生物碱。它们的特点是具有有趣的生物活性，例如针对不同人类癌细胞系（包括多重耐药细胞系）的显着细胞毒性。尽管如此，由于生物碱的高亲脂性，这些衍生物与严重的神经毒性和体内活性丧失有关。在这里，我们描述了安托芬和泰洛福林的高极性前药作为缺氧靶向前药的开发。所开发的菲并吲哚里西啶季铵盐表现出高化学和代谢稳定性，预计不会透过血脑屏障。在常氧条件下测试时，设计的前药显示出降低的细胞毒性。然而，在缺氧条件下测试时，它们的细胞毒性活性显着增加。

  DOI：

  10.3390/molecules26113327
• 作为产物：
  描述：

  1,5-二甲基-4-硝基咪唑 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以75%的产率得到5-(溴甲基)-1-甲基-4-硝基-1H-咪唑
  参考文献：
  名称：

  Synthesis of substituted 5-bromomethyl-4-nitroimidazoles and use for the preparation of the hypoxia-selective multikinase inhibitor SN29966

  摘要：

  5-Bromomethyl-4-nitroimidazoles have utility as bioreductive trigger precursors for the preparation of hypoxia-selective prodrugs. Here we describe an efficient two-step synthesis of 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole, a preferred precursor, employing an N-bromosuccinimide mediated radical bromination. Use of this precursor to prepare SN29966, a promising hypoxia-selective irreversible pan-ErbB inhibitor is reported along with the preparation of four other prodrug candidates. 5-Bromomethyl-4-nitroimidazole analogues bearing electron-donating and electron-withdrawing substituents at the N-1 and C-2 positions are also described. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.08.037

文献信息

• [EN] NOVEL AMINOPYRIDINES AND THEIR USE IN TREATING CANCER<br/>[FR] NOUVELLES AMINOPYRIDINES ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2022064430A1

  公开（公告）日：2022-03-31

  The invention relates to substituted imidazo[4,5-c]pyridine-2-one compounds of Formula (I) and prodrugs of said compounds. Compounds of Formula (I) selectively inhibit the activity of DNA-dependent protein kinase (DNA-PK) and are therefore useful in the treatment of diseases in which inhibition of DNA-PK is beneficial.

  这项发明涉及Formula (I)的取代咪唑并[4,5-c]吡啶-2-酮化合物以及这些化合物的前药。Formula (I)的化合物选择性地抑制DNA-依赖性蛋白激酶(DNA-PK)的活性，因此在治疗需要抑制DNA-PK的疾病中具有用处。
• [EN] FGFR KINASE INHIBITORS AND PHARMACEUTICAL USES<br/>[FR] INHIBITEURS DE KINASE FGFR ET UTILISATIONS PHARMACEUTIQUES
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2018160076A1

  公开（公告）日：2018-09-07

  Fibroblast Growth Factor Receptor kinase inhibitors and prodrugs thereof of Formula (I) and their use for the treatment of hyper-proliferative diseases such as retinopathy, psoriasis, rheumatoid arthritis, osteoarthritis, septic arthritis, tumour metastasis, periodontal disease, cornal ulceration, proteinuria, coronary thrombosis from atherosclerotic plaque, aneurismal aorta, dystrophobic epidermolysis bullosa, degenerative cartilage loss following traumatic joint injury, osteopenias mediated by MMP activity, tempero mandibular joint disease, and demyelating disease of the nervous system.

  纤维母细胞生长因子受体激酶抑制剂及其前药的化学式(I)以及它们用于治疗过度增殖性疾病，如视网膜病变、牛皮癣、类风湿关节炎、骨关节炎、化脓性关节炎、肿瘤转移、牙周病、角膜溃疡、蛋白尿、由动脉粥样硬化斑块引起的冠状动脉血栓形成、主动脉瘤、皮肤表皮溃疡性萎缩性疾病、创伤性关节损伤后的退行性软骨丢失、由MMP活性介导的骨质疏松、颞下颌关节疾病以及神经系统脱髓鞘疾病。
• 4-Nitroimidazole-3-hydroxyflavone conjugate as a fluorescent probe for hypoxic cells
  作者：Weipei Feng、Yuechai Wang、Shizhu Chen、Chao Wang、Shuxiang Wang、Shenghui Li、Hongyan Li、Guoqiang Zhou、Jinchao Zhang

  DOI：10.1016/j.dyepig.2016.03.019

  日期：2016.8

  detection limit (S/N = 3) for NTR was 63 ng/mL. This probe displayed desired properties such as high selectivity, “Turn-On” fluorescence response with suitable sensitivity, no cytotoxicity, large Stokes’ shift, and dual emission. This probe was successfully applied for imaging the hypoxic status of tumor cells (e.g. HeLa cells). We hope to apply this novel probe in the biomedical research fields for the imaging

  用于选择性检测缺氧或硝基还原酶（NTR），2-（4-（二甲基氨基）苯基）-3-（（1-甲基-4-硝基-1H-咪唑-5-基）甲氧基）的新型离线荧光探针-6,8-双（吗啉代甲基）-4H-铬-4--4-酮（3-HF-NO 2）是使用4-硝基咪唑部分作为缺氧触发条件并将两个吗啉基团在6,8-位引入3-HF支架中而开发的。该设计基于在还原的烟酰胺腺嘌呤二核苷酸（NADH）作为电子供体的情况下NTR催化的4-硝基咪唑部分的还原，然后进行1,6-重排消除并释放游离的3-HF染料。NTR的检出限（S / N = 3）为63 ng / mL。该探针显示出所需的特性，例如高选择性，具有合适灵敏度的“打开”荧光响应，无细胞毒性，大斯托克斯位移和双重发射。该探针已成功应用于成像肿瘤细胞（例如HeLa细胞）的低氧状态。我们希望将这种新颖的探针应用于生物医学研究领域，以对疾病相关的缺氧进行成像。
• PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY
  申请人：Smaill Jeffrey Bruce

  公开号：US20120077811A1

  公开（公告）日：2012-03-29

  The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R 1 is a group of the formula —(CH 2 ) n Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH 2 ) n Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R 2 , R 3 and R 4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R 2 )(R 3 )(R 4 )N, or two of R 2 , R 3 , and R 4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R 2 , R 3 and R 4 may be absent and two of R 2 , R 3 and R 4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

  本发明提供了新型的前药化合物，包括一种激酶抑制剂和一种还原活化的破裂芳香族硝基杂环或芳香族硝基碳杂环触发剂，其中该化合物带有正电荷。在优选实施例中，该化合物为式I：其中：X是任何带负电的反离子；R1是公式—(CH2)nTr的基团，其中Tr是芳香族硝基杂环或芳香族硝基碳杂环，—(CH2)nTr作为还原活化的破裂触发器；n是0到6的整数；R2、R3和R4可以各自独立地选择来自三级胺激酶抑制剂的脂肪族或芳香族基团(R2)(R3)(R4)N，或者R2、R3和R4中的两个可以形成激酶抑制剂的脂肪族或芳香族杂环胺环，或者R2、R3和R4中的一个可以缺失，R2、R3和R4中的两个可以形成激酶抑制剂的芳香族杂环胺环。该发明的化合物可用于治疗增殖性疾病，如癌症。
• Prodrug forms of kinase inhibitors and their use in therapy
  申请人：Smaill Jeffrey Bruce

  公开号：US09073916B2

  公开（公告）日：2015-07-07

  The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R1 is a group of the formula —(CH2)nTr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH2)nTr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R2, R3 and R4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R2)(R3)(R4)N, or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R2, R3 and R4 may be absent and two of R2, R3 and R4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

  本发明提供了新型的前药化合物，其中包含一种激酶抑制剂和一种还原活化的分裂芳香族硝基杂环或芳香族硝基碳环触发剂，该化合物带有正电荷。在优选实施例中，该化合物为公式I：其中：X是任何负电荷的反离子；R1是公式—（CH2）nTr的基团，其中Tr是一种芳香族硝基杂环或芳香族硝基碳环，—（CH2）nTr作为还原活化的分裂触发剂；n是从0到6的整数；R2、R3和R4可以各自独立地选择来自三级胺激酶抑制剂（R2）（R3）（R4）N的脂肪族或芳香族基团，或者R2、R3和R4中的两个可以形成激酶抑制剂的脂肪族或芳香族杂环胺环，或者R2、R3和R4中的一个可能不存在，并且R2、R3和R4中的两个可以形成激酶抑制剂的芳香族杂环胺环。本发明的化合物在治疗癌症等增殖性疾病方面是有用的。