2-Azido-1-[2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one | 1261118-45-9

• 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-Azido-1-[2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one
• CAS: 1261118-45-9
• 化学式: C₁₈H₂₁FN₆O
• 分子量: 356.403
• InChiKey: VYSJXTIQKZMVAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  52.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Azido-1-[2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one 在 palladium on activated charcoal 、 氢气 、 溴 、 溶剂黄146 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 24.5h， 生成 tert-butyl N-[1-[3-bromo-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-methyl-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  Imidazolopiperazines: Lead Optimization of the Second-Generation Antimalarial Agents

  摘要：

  On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the compounds by leveraging the outcome of a set of in vitro metabolic identification studies. The optimized 8,8-dimethyl imidazolopiperazine analogues exhibited improved potency, in vitro metabolic stability profile and, as a result, enhanced oral exposure in vivo in mice. The optimized compounds were found to be more efficacious than the current antimalarials in a malaria mouse model. They exhibit moderate oral exposure in rat pharmacokinetic studies to achieve sufficient multiples of the oral exposure at the efficacious dose in toxicology studies.

  DOI：

  10.1021/jm300041e
• 作为产物：
  描述：

  Ethyl 2-(2-(2-(((benzyloxy)carbonyl)amino)propan-2-yl)-4-(4-fluorophenyl)-1H-imidazol-1-yl)acetate 在 sodium azide 、 硼烷四氢呋喃络合物 、 palladium on activated charcoal 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 75.0h， 生成 2-Azido-1-[2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-methylpropan-1-one
  参考文献：
  名称：

  Imidazolopiperazines: Lead Optimization of the Second-Generation Antimalarial Agents

  摘要：

  On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the compounds by leveraging the outcome of a set of in vitro metabolic identification studies. The optimized 8,8-dimethyl imidazolopiperazine analogues exhibited improved potency, in vitro metabolic stability profile and, as a result, enhanced oral exposure in vivo in mice. The optimized compounds were found to be more efficacious than the current antimalarials in a malaria mouse model. They exhibit moderate oral exposure in rat pharmacokinetic studies to achieve sufficient multiples of the oral exposure at the efficacious dose in toxicology studies.

  DOI：

  10.1021/jm300041e

文献信息

• 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。
• US8557801B2
  申请人：——

  公开号：US8557801B2

  公开（公告）日：2013-10-15