benzyl N-[[5-(4-fluorophenyl)-1H-imidazol-2-yl]methyl]carbamate | 1261118-48-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: benzyl N-[[5-(4-fluorophenyl)-1H-imidazol-2-yl]methyl]carbamate
• CAS: 1261118-48-2
• 化学式: C₁₈H₁₆FN₃O₂
• 分子量: 325.342
• InChiKey: LAKXOWIJFBRTKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  67
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl N-[[5-(4-fluorophenyl)-1H-imidazol-2-yl]methyl]carbamate 在 盐酸 作用下， 以 水 为溶剂， 反应 3.0h， 生成 (4-(4-fluorophenyl)-1H-imidazol-2-yl)methanamine
  参考文献：
  名称：

  Small-Molecule Inhibition of the C. difficile FAS-II Enzyme, FabK, Results in Selective Activity

  摘要：

  Clostridioides difficile infection (CDI) is a leading cause of significant morbidity, mortality, and healthcare-related costs in the United States. After standard therapy, recurrence rates remain high, and multiple recurrences are not uncommon. Causes include treatments employing broad-spectrum agents that disrupt the normal host microbiota, as well as treatment-resistant spore formation by C. difficile. Thus, novel druggable anti-C. difficile targets that promote narrow-spectrum eradication and inhibition of sporulation are desired. As a critical rate-limiting step within the FAS-II bacterial fatty acid synthesis pathway, which supplies precursory component phospholipids found in bacterial cytoplasmic and spore-mediated membranes, enoyl-acyl carrier protein (ACP) reductase II (FabK) represents such a target. FabK is essential in C. difficile (CdFabK) and is structurally and mechanistically distinct from other isozymes found in gut microbiota species, making CdFabK an attractive narrow-spectrum target. We report here the kinetic evaluation of CdFabK, the biochemical activity of a series of phenylimidazole analogues, and microbiological data suggesting these compounds' selective antibacterial activity against C. difficile versus several other prominent gut organisms. The compounds display promising, selective, low micromolar CdFabK inhibitory activity without significantly affecting the growth of other gut organisms, and the series prototype (1b) is shown to be competitive for the CdFabK cofactor and uncompetitive for the substrate. A series analogue (1g) shows maintained inhibitory activity while also possessing increased solubility. These findings represent the basis for future drug discovery efforts by characterizing the CdFabK enzyme while demonstrating its druggability and potential role as a narrow-spectrum antidifficile target.

  DOI：

  10.1021/acschembio.9b00293
• 作为产物：
  描述：

  N-苄氧羰基氨基乙腈 在 sodium methylate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 98.0h， 生成 benzyl N-[[5-(4-fluorophenyl)-1H-imidazol-2-yl]methyl]carbamate
  参考文献：
  名称：

  Small-Molecule Inhibition of the C. difficile FAS-II Enzyme, FabK, Results in Selective Activity

  摘要：

  Clostridioides difficile infection (CDI) is a leading cause of significant morbidity, mortality, and healthcare-related costs in the United States. After standard therapy, recurrence rates remain high, and multiple recurrences are not uncommon. Causes include treatments employing broad-spectrum agents that disrupt the normal host microbiota, as well as treatment-resistant spore formation by C. difficile. Thus, novel druggable anti-C. difficile targets that promote narrow-spectrum eradication and inhibition of sporulation are desired. As a critical rate-limiting step within the FAS-II bacterial fatty acid synthesis pathway, which supplies precursory component phospholipids found in bacterial cytoplasmic and spore-mediated membranes, enoyl-acyl carrier protein (ACP) reductase II (FabK) represents such a target. FabK is essential in C. difficile (CdFabK) and is structurally and mechanistically distinct from other isozymes found in gut microbiota species, making CdFabK an attractive narrow-spectrum target. We report here the kinetic evaluation of CdFabK, the biochemical activity of a series of phenylimidazole analogues, and microbiological data suggesting these compounds' selective antibacterial activity against C. difficile versus several other prominent gut organisms. The compounds display promising, selective, low micromolar CdFabK inhibitory activity without significantly affecting the growth of other gut organisms, and the series prototype (1b) is shown to be competitive for the CdFabK cofactor and uncompetitive for the substrate. A series analogue (1g) shows maintained inhibitory activity while also possessing increased solubility. These findings represent the basis for future drug discovery efforts by characterizing the CdFabK enzyme while demonstrating its druggability and potential role as a narrow-spectrum antidifficile target.

  DOI：

  10.1021/acschembio.9b00293

文献信息

• An efficient, stereocontrolled and versatile synthetic route to bicyclic partially saturated privileged scaffolds
  作者：Hannah L. Stewart、Abigail R. Hanby、Thomas A. King、Andrew D. Bond、Thomas A. Moss、Hannah F. Sore、David R. Spring

  DOI：10.1039/d0cc02728f

  日期：——

  development of a simple, high yielding and stereocontrolled strategy for the synthesis of a series of triazolopiperazines and other biologically relevant fused scaffolds from optically active amino acids. This route was applied to the synthesis of 22 scaffolds containing new, previously inaccessible vectors and used to access a novel analogue of ganaplacide.

  在本文中，我们描述了一种简单，高产量和立体控制策略的开发，该策略用于从光学活性氨基酸合成一系列三唑并哌嗪和其他生物学相关的融合支架。该途径被应用于22个含有新的，以前难以接近的载体的支架的合成，并被用于获得一种新的ganaplacide类似物。
• COMPOUNDS AND COMPOSITIONS USEFUL FOR THE TREATMENT OF PARASITIC DISEASES
  申请人：Chatterjee Arnab K.

  公开号：US20110059934A1

  公开（公告）日：2011-03-10

  The invention provides a class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.

  本发明提供了一类化合物，包括该类化合物的药物组合物以及使用该类化合物治疗或预防疟疾的方法。
• COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
  申请人：Chatterjee Arnab K.

  公开号：US20130281403A1

  公开（公告）日：2013-10-24

  The invention provides a class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.

  本发明提供了一类化合物，包括该类化合物的药物组合物和使用该类化合物治疗或预防疟疾的方法。
• COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASE
  申请人：Chatterjee Arnab K.

  公开号：US20160108051A1

  公开（公告）日：2016-04-21

  The invention provides a class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.

  本发明提供了一类化合物，包括这些化合物的药物组合物和使用这些化合物治疗或预防疟疾的方法。
• Imidazo[1,2a]pyrazines and compositions comprising them for the treatment of parasitic diseases
  申请人：IRM LLC

  公开号：EP2737927A1

  公开（公告）日：2014-06-04

  The invention provides compounds of formula Ia, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.

  本发明提供了式 Ia 化合物、包含此类化合物的药物组合物以及使用此类化合物治疗或预防疟疾的方法。