N-((R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxybutyl)-N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitro-2-((S)-pent-4-en-2-yloxy)benzamide | 1403480-66-9

• 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-((R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxybutyl)-N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitro-2-((S)-pent-4-en-2-yloxy)benzamide
• CAS: 1403480-66-9
• 化学式: C₃₄H₄₂FN₃O₉S
• 分子量: 687.787
• InChiKey: JCWSXWJMLIBDAN-IALVYGIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.21
• 重原子数：
  48.0
• 可旋转键数：
  19.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  148.75
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N-((R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxybutyl)-N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitro-2-((S)-pent-4-en-2-yloxy)benzamide 在 Hoveyda-Grubbs catalyst second generation 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 53.5h， 生成 N-(((2S,8R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-11-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2-methyl-12-oxo-2,3,4,5,6,8,9,10,11,12-decahydrobenzo[b][1,9,5]dioxaazacyclotetradecin-8-yl)methyl)-4-fluoro-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-((R)-3-((tert-butyldimethylsilyl)oxy)-4-(4-fluoro-N-methylphenylsulfonamido)butyl)-N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitro-2-((S)-pent-4-en-2-yloxy)benzamide 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以79%的产率得到N-((R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxybutyl)-N-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-5-nitro-2-((S)-pent-4-en-2-yloxy)benzamide
  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