N-((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-3-((2S)-pent-4-en-2-yloxy)pyrazine-2-carboxamide | 1403480-80-7

• 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: N-((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-3-((2S)-pent-4-en-2-yloxy)pyrazine-2-carboxamide
• 英文别名: N-((2R,3R)-3-allyloxy-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)-N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-3-((S)-pent-4-en-2yloxy)pyrazine-2-carboxamide
• CAS: 1403480-80-7
• 化学式: C₃₆H₄₇FN₄O₇S
• 分子量: 698.856
• InChiKey: CKPAMBAWXVPGQR-VQSVPOMMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.54
• 重原子数：
  49.0
• 可旋转键数：
  21.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  120.39
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N-((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-3-((2S)-pent-4-en-2-yloxy)pyrazine-2-carboxamide 在 Hoveyda-Grubbs catalyst second generation 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以95%的产率得到4-fluoro-N-(((6S,12R,13R,E)-15-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-6,13-dimethyl-16-oxo-6,7,10,12,13,14,15,16-octahydropyrazino[2,3-b][1,9,5]dioxaazacyclotetradecin-12-yl)methyl)-N-methylbenzenesulfonamide
  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：

  N-((2R,3R)-2-((tert-butyldimethylsilyl)oxy)-4-(((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)amino)-3-methylbutyl)-4-fluoro-N-methylbenzenesulfonamide 在 四丁基氟化铵 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.5h， 生成 N-((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-3-((2S)-pent-4-en-2-yloxy)pyrazine-2-carboxamide
  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