tert-butyl N-[2-[2-(4-fluorophenyl)-5,5-dimethyl-6,8-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl]carbamate | 1374005-22-7

• 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: tert-butyl N-[2-[2-(4-fluorophenyl)-5,5-dimethyl-6,8-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl]carbamate
• CAS: 1374005-22-7
• 化学式: C₂₁H₂₇FN₄O₃
• 分子量: 402.469
• InChiKey: UGTWAYHOOZKTAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 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：

  tert-butyl N-[2-[2-(4-fluorophenyl)-5,5-dimethyl-6,8-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl]carbamate 在 溴 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以90%的产率得到tert-butyl N-[2-[3-bromo-2-(4-fluorophenyl)-5,5-dimethyl-6,8-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl]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：

  2-(4-fluorophenyl)-7-[(4-methoxyphenyl)methyl]-5,5-dimethyl-8H-imidazo[1,2-a]pyrazin-6-one 在 硼烷四氢呋喃络合物 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 tert-butyl N-[2-[2-(4-fluorophenyl)-5,5-dimethyl-6,8-dihydroimidazo[1,2-a]pyrazin-7-yl]-2-oxoethyl]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