tert-butyl ((2R,3R)-2-hydroxy-4-(N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-((S)-pent-4-en-2-yloxy)-4-(trifluoromethyl)benzamido)-3-methylbutyl)(methyl)carbamate | 1403480-56-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl ((2R,3R)-2-hydroxy-4-(N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-((S)-pent-4-en-2-yloxy)-4-(trifluoromethyl)benzamido)-3-methylbutyl)(methyl)carbamate
• CAS: 1403480-56-7
• 化学式: C₃₅H₄₉F₃N₂O₇
• 分子量: 666.778
• InChiKey: GMXTZYUUVAAMKN-DUXAABNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.97
• 重原子数：
  47.0
• 可旋转键数：
  16.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  97.77
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl ((2R,3R)-2-hydroxy-4-(N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-((S)-pent-4-en-2-yloxy)-4-(trifluoromethyl)benzamido)-3-methylbutyl)(methyl)carbamate 在 Hoveyda-Grubbs catalyst second generation 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 生成 tert-butyl (((2S,8R,9R,E/Z)-11-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2,9-dimethyl-12-oxo-15-(trifluoromethyl)-2,3,6,8,9,10,11,12-octahydrobenzo[b][1,9,5]dioxaazacyclotetradecin-8-yl)methyl)(methyl)carbamate
  参考文献：
  名称：

  Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents

  摘要：

  Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure-activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.

  DOI：

  10.1021/jm500994n
• 作为产物：
  描述：

  tert-butyl ((2R,3S)-2-((tert-butyldimethylsilyl)oxy)-4-(((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)amino)-3-methyl-4-oxobutyl)(methyl)carbamate 在 四丁基氟化铵 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 tert-butyl ((2R,3R)-2-hydroxy-4-(N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-((S)-pent-4-en-2-yloxy)-4-(trifluoromethyl)benzamido)-3-methylbutyl)(methyl)carbamate
  参考文献：
  名称：

  Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents

  摘要：

  Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure-activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.

  DOI：

  10.1021/jm500994n