2-(but-3-en-1-yloxy)-N-((2R,3R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxy-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitrobenzenesulfonamide | 1403480-61-4

• 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: 2-(but-3-en-1-yloxy)-N-((2R,3R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxy-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitrobenzenesulfonamide
• 英文别名: 2-(but-3-en-1-yloxy)-N-((2R,3R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxy-2-methylbutyl)-N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitrobenzenesulfonamide
• CAS: 1403480-61-4
• 化学式: C₃₃H₄₂FN₃O₁₀S₂
• 分子量: 723.841
• InChiKey: WRJZVOOHYDHLKR-QOMXPILVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.61
• 重原子数：
  49.0
• 可旋转键数：
  20.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  165.82
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2-(but-3-en-1-yloxy)-N-((2R,3R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxy-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitrobenzenesulfonamide 在 Hoveyda-Grubbs catalyst second generation 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 54.0h， 生成 15-amino-4-fluoro-N-(((4R,5R)-2-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-4-methyl-1,1-dioxido-3,4,5,7,8,9,10,11-octahydro-2H-benzo[b][1,9,4,5]dioxathiaazacyclotetradecin-5-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：

  2-(but-3-en-1-yloxy)-N-((2R,3R)-3-((tert-butyldimethylsilyl)oxy)-4-(4-fluoro-Nmethylphenylsulfonamido)-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitrobenzenesulfonamide 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以96%的产率得到2-(but-3-en-1-yloxy)-N-((2R,3R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxy-2-methylbutyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitrobenzenesulfonamide
  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