Carbamic acid, N-[2-[3-bromo-2-(4-fluorophenyl)-5,6-dihydro-8,8-dimethylimidazo[1,2-a]pyrazin-7(8H)-yl]-2-oxoethyl]-, phenylmethyl ester | 1261117-67-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Carbamic acid, N-[2-[3-bromo-2-(4-fluorophenyl)-5,6-dihydro-8,8-dimethylimidazo[1,2-a]pyrazin-7(8H)-yl]-2-oxoethyl]-, phenylmethyl ester
• 英文别名: benzyl N-[2-[3-bromo-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl]carbamate
• CAS: 1261117-67-2
• 化学式: C₂₄H₂₄BrFN₄O₃
• 分子量: 515.382
• InChiKey: GIGRABGCHRZUSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  76.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Carbamic acid, N-[2-[3-bromo-2-(4-fluorophenyl)-5,6-dihydro-8,8-dimethylimidazo[1,2-a]pyrazin-7(8H)-yl]-2-oxoethyl]-, phenylmethyl ester 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 2-(4-fluorophenyl)-8,8-dimethyl-N-p-tolyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-amine
  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：

  Benzyl (2-(4-(4-fluorophenyl)-1H-imidazol-2-YL)propan-2-YL)carbamate 在 硼烷四氢呋喃络合物 、 palladium on activated charcoal 、 氢气 、 溴 、 caesium carbonate 、 溶剂黄146 、 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-) 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 74.5h， 生成 Carbamic acid, N-[2-[3-bromo-2-(4-fluorophenyl)-5,6-dihydro-8,8-dimethylimidazo[1,2-a]pyrazin-7(8H)-yl]-2-oxoethyl]-, phenylmethyl ester
  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

• 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。
• [EN] COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE MALADIES PARASITAIRES
  申请人：IRM LLC

  公开号：WO2011006143A2

  公开（公告）日：2011-01-13

  The invention provides a class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.
• Imidazolopiperazines: Lead Optimization of the Second-Generation Antimalarial Agents
  作者：Advait Nagle、Tao Wu、Kelli Kuhen、Kerstin Gagaring、Rachel Borboa、Caroline Francek、Zhong Chen、David Plouffe、Xuena Lin、Christopher Caldwell、Jared Ek、Suzanne Skolnik、Fenghua Liu、Jianling Wang、Jonathan Chang、Chun Li、Bo Liu、Thomas Hollenbeck、Tove Tuntland、John Isbell、Tiffany Chuan、Philip B. Alper、Christoph Fischli、Reto Brun、Suresh B. Lakshminarayana、Matthias Rottmann、Thierry T. Diagana、Elizabeth A. Winzeler、Richard Glynne、David C. Tully、Arnab K. Chatterjee

  DOI：10.1021/jm300041e

  日期：2012.5.10

  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.