2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine | 889945-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine
• 英文别名: Imidazo[1,2-a]pyrazine, 3-amino-2-(4-fluorophenyl)-
• CAS: 889945-78-2
• 化学式: C₁₂H₉FN₄
• 分子量: 228.229
• InChiKey: HLCONPPRQDXWIG-UHFFFAOYSA-N

物化性质

• 密度：
  1.42±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium on carbon 、 氢气 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-amino-1-(3-(3,5-difluorophenylamino)-2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one
  参考文献：
  名称：

  Imidazolopiperazines: Hit to Lead Optimization of New Antimalarial Agents

  摘要：

  Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant parasites and improvement of physiochemical and pharmacokinetic properties. The lead compounds in this series showed good potencies in vitro and decent oral exposure levels in vivo. In a Plasmodium berghei mouse infection model, one lead compound lowered the parasitemia level by 99.4% after administration of 100 mg/kg single oral dose and prolonged mice survival by an average of 17.0 days. The lead compounds were also well-tolerated in the preliminary in vitro toxicity studies and represents an interesting lead for drug development.

  DOI：

  10.1021/jm2003359
• 作为产物：
  描述：

  N-(tert-butyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以100%的产率得到2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine
  参考文献：
  名称：

  Imidazolopiperazines: Hit to Lead Optimization of New Antimalarial Agents

  摘要：

  Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant parasites and improvement of physiochemical and pharmacokinetic properties. The lead compounds in this series showed good potencies in vitro and decent oral exposure levels in vivo. In a Plasmodium berghei mouse infection model, one lead compound lowered the parasitemia level by 99.4% after administration of 100 mg/kg single oral dose and prolonged mice survival by an average of 17.0 days. The lead compounds were also well-tolerated in the preliminary in vitro toxicity studies and represents an interesting lead for drug development.

  DOI：

  10.1021/jm2003359

文献信息

• A chemoselective Ugi-type reaction in water using TMSCN as a functional isonitrile equivalent: generation of heteroaromatic molecular diversity
  作者：Sankar Kumar Guchhait、Vikas Chaudhary、Chetna Madaan

  DOI：10.1039/c2ob26733k

  日期：——

  KF-mediated nucleophilic activation of TMSCN as a functional isonitrile equivalent establishes an efficient and chemoselective Ugi-type multicomponent reaction of a heterocyclic amidine and aldehyde with TMSCN in water. In this approach, the use of isocyanide is circumvented, known competing reactions are virtually eliminated, pure products are obtained by a non-chromatographic method, and therapeutically relevant and diverse N-fused 3-aminoimidazoles can be prepared from a wide variety of aldehydes and heterocyclic amidines. This reaction coupling with cascade cyclization provides various privileged tetracyclic heteroaromatic scaffolds.

  KF催化的TMSCN亲核活化作为功能性异腈等价物，建立了羟基胺和醛与TMSCN在水中进行的高效且化学选择性的Ugi类型多组分反应。在这种方法中，避免了异氰酸酯的使用，已知的竞争反应几乎被消除，纯产品通过非色谱法获得，并且可从多种醛和杂环胺制备出具有治疗相关性和多样性的N-融合3-氨基咪唑。该反应结合级联环化提供了多种特权的四环杂芳烃骨架。
• 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。