1-isopropyl-6-methoxy-4-nitro-1H-benzo[d]imidazole | 1173202-48-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-isopropyl-6-methoxy-4-nitro-1H-benzo[d]imidazole
• 英文别名: 6-Methoxy-4-nitro-1-propan-2-ylbenzimidazole；6-methoxy-4-nitro-1-propan-2-ylbenzimidazole
• CAS: 1173202-48-6
• 化学式: C₁₁H₁₃N₃O₃
• 分子量: 235.243
• InChiKey: BUGJTHHZYLYZQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-isopropyl-6-methoxy-4-nitro-1H-benzo[d]imidazole 在 氢溴酸 作用下， 反应 2.5h， 以97%的产率得到1-isopropyl-4-nitro-1H-benzo[d]imidazol-6-ol
  参考文献：
  名称：

  基于苯并咪唑的丝裂原活化激酶5信号通路选择性抑制剂的构效关系

  摘要：

  在先前的交流中，我们鉴定了一种新型的基于苯并咪唑的EGF诱导的ERK5磷酸化抑制剂。在本文中，我们研究了几种基于1-异丙基-4-氨基-6-醚连接的苯并咪唑类化合物的生物活性，以选择性抑制EGF介导的ERK5磷酸化。最初的结构特征调查显示了6位变异的潜在效用。通过蛋白质印迹分析分析了EGF诱导的HEK293细胞中pERK1 / 2和pERK5形成的修饰。随后介绍了在高通量多重激酶扫描和NCI 60细胞株筛选中所选化合物的分析。

  DOI：

  10.1016/j.bmc.2010.09.017
• 作为产物：
  描述：

  甲酸 、 在 盐酸 、 2,6-二叔丁基-4-甲基苯酚 、 sodium hydroxide 作用下， 以 水 为溶剂， 以4.5 g的产率得到1-isopropyl-6-methoxy-4-nitro-1H-benzo[d]imidazole
  参考文献：
  名称：

  Design, synthesis, and testing of an 6-O-linked series of benzimidazole based inhibitors of CDK5/p25

  摘要：

  Alzheimer's disease (AD) is a progressive neurodegenerative disease resulting in cognitive and behavioral impairment. The two classic pathological hallmarks of AD include extraneuronal deposition of amyloid beta (A beta) and intraneuronal formation of neurofibrillary tangles (NFTs). NFTs contain hyperphosphorylated tau. Tau is the major microtubule-associated protein in neurons and stabilizes microtubules (MTs). Cyclin dependent kinase 5 (CDK5), when activated by the regulatory binding protein p25, phosphorylates tau at a number of proline-directed serine/threonine residues, resulting in formation of phosphorylated tau as paired helical filaments (PHFs) then in subsequent deposition of PHFs as NFTs. Beginning with the structure of Roscovitine, a moderately selective CDK5 inhibitor, we sought to conduct structural modifications to increase inhibitory potency of CDK5 and increase selectivity over a similar enzyme, cyclin dependent kinase 2 (CDK2). The design, synthesis, and testing of a series of 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles is presented. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.022

文献信息

• Structure–activity relationships of benzimidazole-based selective inhibitors of the mitogen activated kinase-5 signaling pathway
  作者：Patrick T. Flaherty、Ishveen Chopra、Prashi Jain、Darlene Monlish、Jane Cavanaugh

  DOI：10.1016/j.bmc.2010.09.017

  日期：2010.11.15

  In a prior communication we identified a novel class of benzimidazole-based inhibitors of EGF-induced phosphorylation of ERK5. In this paper we examine the biological activity of several 1-isopropyl-4-amino-6-ether linked benzimidazole-based compounds for their ability to selectively inhibit EGF-mediated ERK5 phosphorylation; potential utility of variation at the 6-position was indicated by the initial

  在先前的交流中，我们鉴定了一种新型的基于苯并咪唑的EGF诱导的ERK5磷酸化抑制剂。在本文中，我们研究了几种基于1-异丙基-4-氨基-6-醚连接的苯并咪唑类化合物的生物活性，以选择性抑制EGF介导的ERK5磷酸化。最初的结构特征调查显示了6位变异的潜在效用。通过蛋白质印迹分析分析了EGF诱导的HEK293细胞中pERK1 / 2和pERK5形成的修饰。随后介绍了在高通量多重激酶扫描和NCI 60细胞株筛选中所选化合物的分析。
• Identification of benzimidazole-based inhibitors of the mitogen activated kinase-5 signaling pathway
  作者：Patrick T. Flaherty、Ishveen Chopra、Prashi Jain、Shuyan Yi、Erika Allen、Jane Cavanaugh

  DOI：10.1016/j.bmcl.2010.03.033

  日期：2010.5

  The MEK-signaling pathways are complex but critical signaling cascades that correlate an extracellular signaling event with internal cell processes. To date at least seven MEK isozymes have been identified. MEK5, in particular, is upregulated in multiple forms of tumors. Analysis of the EGF-induced MEK5 signaling cascade in cultured HEK cells has identified compounds that can inhibit MEK5 phosphorylation of ERK5; observed biological activity is dependent on chemical variation. (C) 2010 Elsevier Ltd. All rights reserved.
• Design, synthesis, and testing of an 6-O-linked series of benzimidazole based inhibitors of CDK5/p25
  作者：Prashi Jain、Patrick T. Flaherty、Shuyan Yi、Ishveen Chopra、Gwenyth Bleasdell、Josh Lipay、Yoan Ferandin、Laurent Meijer、Jeffry D. Madura

  DOI：10.1016/j.bmc.2010.11.022

  日期：2011.1

  Alzheimer's disease (AD) is a progressive neurodegenerative disease resulting in cognitive and behavioral impairment. The two classic pathological hallmarks of AD include extraneuronal deposition of amyloid beta (A beta) and intraneuronal formation of neurofibrillary tangles (NFTs). NFTs contain hyperphosphorylated tau. Tau is the major microtubule-associated protein in neurons and stabilizes microtubules (MTs). Cyclin dependent kinase 5 (CDK5), when activated by the regulatory binding protein p25, phosphorylates tau at a number of proline-directed serine/threonine residues, resulting in formation of phosphorylated tau as paired helical filaments (PHFs) then in subsequent deposition of PHFs as NFTs. Beginning with the structure of Roscovitine, a moderately selective CDK5 inhibitor, we sought to conduct structural modifications to increase inhibitory potency of CDK5 and increase selectivity over a similar enzyme, cyclin dependent kinase 2 (CDK2). The design, synthesis, and testing of a series of 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles is presented. (C) 2010 Elsevier Ltd. All rights reserved.
• Suzuki-Miyaura Cross-Coupling of Potassium Organoborates with 6-Sulfonate Benzimidazoles Using Microwave Irradiation
  作者：Prashi Jain、Shuyan Yi、Patrick Thomas Flaherty

  DOI：10.1002/jhet.1109

  日期：2013.2

  partners for Suzuki–Miyaura cross-coupling with 4-nitro-6-triflyl benzimidazoles using microwave irradiation. The C–C bond formation at the 6-position of the electron-rich 1-,4-,6-trisubstituted benzimidazole core is challenging and was not achievable via Kumada, Negishi, Stille, or Heck coupling strategies. Yields of 37–70% could be obtained via palladium coupling strategies utilizing potassium benzyl trifluoroborates

  本文重点介绍了有机三氟硼酸盐作为铃木-宫浦与4-硝基-6-三氟苯并咪唑类化合物在微波辐射下交叉偶联的偶联伴侣的应用。在富电子的1,4-，6-三取代的苯并咪唑核心的6位上形成C–C键具有挑战性，并且无法通过Kumada，Negishi，Stille或Heck偶联策略实现。通过使用三氟硼酸苄基钾作为有机金属偶合伙伴的钯偶合策略可以获得37-70％的产率。