4-fluoro-N-(((7R,8R,14S)-5-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-1,7,14-trimethyl-4-oxo-4,5,6,7,8,10,11,12,13,14-decahydro-1H-pyrazolo[3,4-b][1,9,5]dioxaazacyclotetradecin-8-yl)methyl)-N-methylbenzenesulfonamide | 1403478-58-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 4-fluoro-N-(((7R,8R,14S)-5-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-1,7,14-trimethyl-4-oxo-4,5,6,7,8,10,11,12,13,14-decahydro-1H-pyrazolo[3,4-b][1,9,5]dioxaazacyclotetradecin-8-yl)methyl)-N-methylbenzenesulfonamide
• 英文别名: 4-fluoro-N-(((7R,8R,14S)-5-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-1,7,14-trimethyl-4-oxo-4,5,6,7,8,10,11,12,13,14-decahydro-1H-pyrazolo[3,4-b][1,9,5]dioxaazacyclotetradecin-8-yl)methyl)-N-methylbenzenesulfonamide；4-fluoro-N-[[(3S,9R,10R)-12-[(2S)-1-[(4-methoxyphenyl)methoxy]propan-2-yl]-3,10,17-trimethyl-13-oxo-2,8-dioxa-12,16,17-triazabicyclo[12.3.0]heptadeca-1(14),15-dien-9-yl]methyl]-N-methylbenzenesulfonamide
• CAS: 1403478-58-9
• 化学式: C₃₄H₄₇FN₄O₇S
• 分子量: 674.834
• InChiKey: RJMDDZYBUXQWIH-UJFVLINRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 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 Wilkinson's catalyst 、 Hoveyda-Grubbs catalyst second generation 、 四丁基氟化铵 、 氢气 、 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 、 甲苯 、 叔丁醇 为溶剂， 生成 4-fluoro-N-(((7R,8R,14S)-5-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-1,7,14-trimethyl-4-oxo-4,5,6,7,8,10,11,12,13,14-decahydro-1H-pyrazolo[3,4-b][1,9,5]dioxaazacyclotetradecin-8-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