2-chloromethyl-1-methyl-4-nitro-1H-imidazole | 118467-52-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloromethyl-1-methyl-4-nitro-1H-imidazole
• 英文别名: 2-(chloromethyl)-1-methyl-4-nitroimidazole；1-methyl 2-chloromethyl 4-nitroimidazole；2-(chloromethyl)-1-methyl-4-nitro-1H-imidazole
• CAS: 118467-52-0
• 化学式: C₅H₆ClN₃O₂
• 分子量: 175.575
• InChiKey: YDWIWDAQXAVDBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 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：

  2-chloromethyl-1-methyl-4-nitro-1H-imidazole 在 lithium bromide 作用下， 以 丙酮 为溶剂， 反应 5.0h， 以95%的产率得到2-(bromomethyl)-1-methyl-4-nitro-1H-imidazole
  参考文献：
  名称：

  [EN] PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY
  [FR] FORMES PROMÉDICAMENTS D'INHIBITEURS DE KINASE ET LEUR UTILISATION EN THÉRAPIE

  摘要：

  公开号：

  WO2010104406A8
• 作为产物：
  描述：

  N-甲基咪唑 生成 2-chloromethyl-1-methyl-4-nitro-1H-imidazole
  参考文献：
  名称：

  CROZET, MICHEL P.;VANELLE, PATRICE;JENTZER, OLIVIER;MALDONADO, JOSE, C. R. ACAD. SCI. SER. 2, 306,(1988) N 14, C. 967-988

  摘要：

  DOI：

文献信息

• Compounds containing 2-substituted imidazole ring for treatment against human African trypanosomiasis
  作者：Bhupesh S. Samant、Mugdha G. Sukhthankar

  DOI：10.1016/j.bmcl.2010.12.040

  日期：2011.2

  A series of compounds containing 2-substituted imidazoles has been synthesized from imidazole and tested for its biological activity against human African trypanosomiasis (HAT). The 2-substituted 5-nitroimidazoles such as fexinidazole (7a) and 1-[4-(1-methyl-5-nitro-1H-imidazol-2-ylmethoxy)-pyridin-2-yl-piperazine (9e) exhibited potent activity against T. brucei in vitro with low cytotoxicity and good

  由咪唑合成了一系列含有2-取代的咪唑的化合物，并对其抗人类非洲锥虫病（HAT）的生物学活性进行了测试。2-取代的5-硝基咪唑，如非那唑（7a）和1- [4-（1-甲基-5-硝基-1 H-咪唑-2-基甲氧基）-吡啶-2-基-哌嗪（9e）表现出强效具有体外抗布鲁氏杆菌的活性，具有低细胞毒性和良好的溶解性。在2-取代的咪唑中，在咪唑环的5位上存在NO 2基团是抑制布鲁氏菌的关键因素。
• Hypoxia-Selective Antitumor Agents. 16. Nitroarylmethyl Quaternary Salts as Bioreductive Prodrugs of the Alkylating Agent Mechlorethamine
  作者：Moana Tercel、Alan E. Lee、Alison Hogg、Robert F. Anderson、Ho H. Lee、Bronwyn G. Siim、William A. Denny、William R. Wilson

  DOI：10.1021/jm010202l

  日期：2001.10.1

  Nitrobenzyl quaternary salts of nitrogen mustards have been previously reported as hypoxia-selective cytotoxins. In this paper we describe the synthesis and evaluation of a series of heterocyclic analogues, including pyrrole, imidazole, thiophene, and pyrazole examples, chosen to cover a range of one-electron reduction potentials (from -277 to -511 mV) and substitution patterns. All quaternary salt

  氮芥子碱的硝基苄基季盐先前已报道为低氧选择性细胞毒素。在本文中，我们描述了一系列杂环类似物的合成和评估，包括吡咯，咪唑，噻吩和吡唑的例子，这些例子被选择来涵盖一系列单电子还原电势（从-277至-511 mV）和取代模式。所有季盐化合物在体外的毒性均比甲乙胺低，并且在低氧条件下的毒性都比有氧条件下的毒性更高，尽管该系列中的差异差异很大。最有希望的类似物咪唑2在低氧的RIF-1细胞中表现出选择性的DNA交联，并且在体内与放射线或顺铂联合具有活性。但是，2在体内也产生了无法预测的毒性，
• 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。
• Nouveaux 5-nitroimidazoles à noyau lactame hautement actifs : préparation et propriétés antibactériennes
  作者：O Jentzer、P Vanelle、MP Crozet、J Maldonado、M Barreau

  DOI：10.1016/0223-5234(91)90118-7

  日期：1991.10

  New 5-nitroimidazoles bearing a trisubstituted ethylenic double bond in position 2 were prepared by reacting various 1-alkyl-2-chloromethyl-5-nitroimidazole with 3-nitrolactam anions by S(RN)1 mechanism in phase-transfer catalysis conditions. These compounds showed in vitro and in vivo antianaerobic activity which was clearly greater than that of metronidazole. Structure-activity relationships have been discussed.