tert-butyl (((8R,9R,15S)-6-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-8,15-dimethyl-5-oxo-5,6,7,8,9,11,12,13,14,15-decahydropyrido[2,3-b][1,9,5]dioxaazacyclotetradecin-9-yl)methyl)(methyl)carbamate | 1403481-51-5

• 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: tert-butyl (((8R,9R,15S)-6-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-8,15-dimethyl-5-oxo-5,6,7,8,9,11,12,13,14,15-decahydropyrido[2,3-b][1,9,5]dioxaazacyclotetradecin-9-yl)methyl)(methyl)carbamate
• CAS: 1403481-51-5
• 化学式: C₃₄H₅₁N₃O₇
• 分子量: 613.795
• InChiKey: MKHOTCWGVRUPSB-MGLAESSXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.98
• 重原子数：
  44.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  99.66
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (((8R,9R,15S)-6-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-8,15-dimethyl-5-oxo-5,6,7,8,9,11,12,13,14,15-decahydropyrido[2,3-b][1,9,5]dioxaazacyclotetradecin-9-yl)methyl)(methyl)carbamate 在 2,6-二甲基吡啶 、 叠氮磷酸二苯酯 、 氟化氢吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 N-(((8R,9R,15S)-6-((2S)-1-aminopropan-2-yl)-8,15-dimethyl-5-oxo-5,6,7,8,9,11,12,13,14,15-decahydropyrido[2,3-b][1,9,5]dioxaazacyclotetradecin-9-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：

  2-氯烟酸叔丁酯 在 Hoveyda-Grubbs catalyst second generation 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 sodium hexamethyldisilazane 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 sodium hydride 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 、 mineral oil 为溶剂， 反应 69.0h， 生成 tert-butyl (((8R,9R,15S)-6-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-8,15-dimethyl-5-oxo-5,6,7,8,9,11,12,13,14,15-decahydropyrido[2,3-b][1,9,5]dioxaazacyclotetradecin-9-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