5-bromo-1-propyl-1H-benzo[d]imidazol-2-amine

• 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: 5-bromo-1-propyl-1H-benzo[d]imidazol-2-amine
• 英文别名: 5-Bromo-1-propylbenzimidazol-2-amine
• 化学式: C₁₀H₁₂BrN₃
• 分子量: 254.129
• InChiKey: BYSCHNHIQUTFEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1-propyl-1H-benzo[d]imidazol-2-amine 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 双氧水 、 palladium diacetate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三(邻甲基苯基)磷 、 sodium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 92.0h， 生成 3-[2-[(3-Carbamoylbenzoyl)amino]-1-propylbenzimidazol-5-yl]propanoic acid
  参考文献：
  名称：

  Plasmodium PK9 Inhibitors Promote Growth of Liver-Stage Parasites

  摘要：

  There is a scarcity of pharmacological tools to interrogate protein kinase function in Plasmodium parasites, the causative agent of malaria. Among Plasmodium's protein kinases, those characterized as atypical represent attractive drug targets as they lack sequence similarity to human proteins. Here, we describe takinib as a small molecule to bind the atypical P. falciparum protein kinase 9 (PfPK9). PfPK9 phosphorylates the Plasmodium E2 ubiquitin-conjugating enzyme PfUBC13, which mediates K63-linkage-specific polyubiquitination. Takinib is a potent human TAK1 inhibitor, thus we developed the Plasmodium-selective takinib analog HS220. We demonstrate that takinib and HS220 decrease K63-linked ubiquitination in P. falciparum, suggesting PfPK9 inhibition in cells. Takinib and HS220 induce a unique phenotype where parasite size in hepatocytes increases, yet high compound concentrations decrease the number of parasites. Our studies highlight the role of PK9 in regulating parasite development and the potential of targeting Plasmodium kinases for malaria control.

  DOI：

  10.1016/j.chembiol.2018.11.003
• 作为产物：
  描述：

  4-溴-1-氟-2-硝基苯 在 10% Pt/activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 162.0h， 生成 5-bromo-1-propyl-1H-benzo[d]imidazol-2-amine
  参考文献：
  名称：

  新型苯并咪唑苯基乙酰胺作为广谱锥虫的全过程优化

  摘要：

  克鲁氏锥虫和布鲁氏锥虫分别是恰加斯氏病和人类非洲锥虫病（HAT）的寄生病原体。当前用于治疗这些疾病的药物对于所有阶段和/或寄生虫亚种并不是有效的，经常表现出副作用。本文中，我们报告了先前从高通量筛选中发现的针对T. cruzi，布鲁氏锥虫的新型命中的2-（4-氯苯基）-N-（1-丙基-1 H-苯并咪唑-2-基）乙酰胺的SAR探索。布鲁西和利什曼原虫。合成了一组信息丰富的类似物，其中掺入了支架的关键修饰，从而提高了效力，而大多数化合物对H9c2和HEK293细胞系保留了低细胞毒性。针对克氏锥虫观察到的SAR与针对Tb brucei观察到的SAR大致相同，这表明有可能使用广谱候选物。因此，这类化合物值得进一步研究以开发作为南美锥虫病和HAT的治疗药物。

  DOI：

  10.1039/d0md00058b

文献信息

• Substituted benzimidazoles as inhibitors of transforming growth factor-β kinase
  申请人：Duke University

  公开号：US10927083B2

  公开（公告）日：2021-02-23

  The present invention provides inhibitors of TAK1 having formula (II), affinity resins, and fluorescent dyes and methods of using such compounds to treat various diseases or in protein isolation or purification.

  本发明提供了具有式（II）的 TAK1 抑制剂、亲和树脂和荧光染料，以及使用此类化合物治疗各种疾病或分离或纯化蛋白质的方法。
• SUBSTITUTED BENZIMIDAZOLE AND BENZOTHIAZOLE INHIBITORS OF TRANSFORMING GROWTH FACTOR-BETA KINASE AND METHODS OF USE THEREOF
  申请人：Duke University

  公开号：US20190263759A1

  公开（公告）日：2019-08-29

  The present invention provides inhibitors of TAK1 having formula (II), affinity resins, and fluorescent dyes and methods of using such compounds to treat various diseases or in protein isolation or purification.
• SUBSTITUTED BENZIMIDAZOLES AS INHIBITORS OF TRANSFORMING GROWTH FACTOR-BETA KINASE
  申请人：Duke University

  公开号：US20210188783A1

  公开（公告）日：2021-06-24

  The present invention provides inhibitors of TAK1 having formula (II), affinity resins, and fluorescent dyes and methods of using such compounds to treat various diseases or in protein isolation or purification.
• Hit-to-lead optimization of novel benzimidazole phenylacetamides as broad spectrum trypanosomacides
  作者：Nicole McNamara、Raphael Rahmani、Melissa L. Sykes、Vicky M. Avery、Jonathan Baell

  DOI：10.1039/d0md00058b

  日期：——

  Trypanosoma cruzi and Trypanosoma brucei are the parasitic causative agents of Chagas disease and human African trypanosomiasis (HAT), respectively. The drugs currently used to treat these diseases are not efficacious against all stages and/or parasite sub-species, often displaying side effects. Herein, we report the SAR exploration of a novel hit, 2-(4-chlorophenyl)-N-(1-propyl-1H-benzimidazol-2-yl)acetamide

  克鲁氏锥虫和布鲁氏锥虫分别是恰加斯氏病和人类非洲锥虫病（HAT）的寄生病原体。当前用于治疗这些疾病的药物对于所有阶段和/或寄生虫亚种并不是有效的，经常表现出副作用。本文中，我们报告了先前从高通量筛选中发现的针对T. cruzi，布鲁氏锥虫的新型命中的2-（4-氯苯基）-N-（1-丙基-1 H-苯并咪唑-2-基）乙酰胺的SAR探索。布鲁西和利什曼原虫。合成了一组信息丰富的类似物，其中掺入了支架的关键修饰，从而提高了效力，而大多数化合物对H9c2和HEK293细胞系保留了低细胞毒性。针对克氏锥虫观察到的SAR与针对Tb brucei观察到的SAR大致相同，这表明有可能使用广谱候选物。因此，这类化合物值得进一步研究以开发作为南美锥虫病和HAT的治疗药物。
• Plasmodium PK9 Inhibitors Promote Growth of Liver-Stage Parasites
  作者：Rene Raphemot、Amber Leigh Eubanks、Maria Toro-Moreno、Rechel Anne Geiger、Philip Floyd Hughes、Kuan-Yi Lu、Timothy Arthur James Haystead、Emily Rose Derbyshire

  DOI：10.1016/j.chembiol.2018.11.003

  日期：2019.3

  There is a scarcity of pharmacological tools to interrogate protein kinase function in Plasmodium parasites, the causative agent of malaria. Among Plasmodium's protein kinases, those characterized as atypical represent attractive drug targets as they lack sequence similarity to human proteins. Here, we describe takinib as a small molecule to bind the atypical P. falciparum protein kinase 9 (PfPK9). PfPK9 phosphorylates the Plasmodium E2 ubiquitin-conjugating enzyme PfUBC13, which mediates K63-linkage-specific polyubiquitination. Takinib is a potent human TAK1 inhibitor, thus we developed the Plasmodium-selective takinib analog HS220. We demonstrate that takinib and HS220 decrease K63-linked ubiquitination in P. falciparum, suggesting PfPK9 inhibition in cells. Takinib and HS220 induce a unique phenotype where parasite size in hepatocytes increases, yet high compound concentrations decrease the number of parasites. Our studies highlight the role of PK9 in regulating parasite development and the potential of targeting Plasmodium kinases for malaria control.