3-[5-(bromomethyl)-4-nitro-1H-imidazol-1-yl]propanamide | 1245556-16-4

• 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-[5-(bromomethyl)-4-nitro-1H-imidazol-1-yl]propanamide
• 英文别名: 5-(Bromomethyl)-4-nitro-1h-imidazole-1-propanamide；3-[5-(bromomethyl)-4-nitroimidazol-1-yl]propanamide
• CAS: 1245556-16-4
• 化学式: C₇H₉BrN₄O₃
• 分子量: 277.077
• InChiKey: HLGXPFSTWPZZJT-UHFFFAOYSA-N

物化性质

• 沸点：
  584.6±45.0 °C(Predicted)
• 密度：
  1.92±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(5-methyl-4-nitro-1H-imidazol-1-yl)propanenitrile 在 N-溴代丁二酰亚胺(NBS) 、 硫酸 作用下， 以 水 、 乙腈 为溶剂， 反应 2.0h， 生成 3-[5-(bromomethyl)-4-nitro-1H-imidazol-1-yl]propanamide
  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

• 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。
• [EN] PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY<br/>[FR] FORMES PROMÉDICAMENTS D'INHIBITEURS DE KINASE ET LEUR UTILISATION EN THÉRAPIE
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2010104406A8

  公开（公告）日：2011-10-06
• US9073916B2
  申请人：——

  公开号：US9073916B2

  公开（公告）日：2015-07-07
• Synthesis of substituted 5-bromomethyl-4-nitroimidazoles and use for the preparation of the hypoxia-selective multikinase inhibitor SN29966
  作者：Guo-Liang Lu、Amir Ashoorzadeh、Robert F. Anderson、Adam V. Patterson、Jeff B. Smaill

  DOI：10.1016/j.tet.2013.08.037

  日期：2013.10

  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.