N-(((6R,7R)-12-(3-(3,5-dimethylisoxazol-4-yl)ureido)-9-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-7-methyl-10-oxo-2,3,4,6,7,8,9,10-octahydrobenzo[f][1,5,9]dioxaazacyclododecin-6-yl)methyl)-4-fluoro-N-methylbenzenesulfonamide | 1403478-68-1

• 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: N-(((6R,7R)-12-(3-(3,5-dimethylisoxazol-4-yl)ureido)-9-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-7-methyl-10-oxo-2,3,4,6,7,8,9,10-octahydrobenzo[f][1,5,9]dioxaazacyclododecin-6-yl)methyl)-4-fluoro-N-methylbenzenesulfonamide
• 英文别名: N-(((6R,7R)-12-(3-(3,5-dimethylisoxazol-4-yl)ureido)-9-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-7-methyl-10-oxo-2,3,4,6,7,8,9,10-octahydrobenzo[f][1,5,9]dioxaazacyclododecin-6-yl)methyl)-4-fluoro-N-methylbenzenesulfonamide；1-(3,5-dimethyl-1,2-oxazol-4-yl)-3-[(7R,8R)-7-[[(4-fluorophenyl)sulfonyl-methylamino]methyl]-10-[(2S)-1-[(4-methoxyphenyl)methoxy]propan-2-yl]-8-methyl-11-oxo-2,6-dioxa-10-azabicyclo[10.4.0]hexadeca-1(12),13,15-trien-14-yl]urea
• CAS: 1403478-68-1
• 化学式: C₃₉H₄₈FN₅O₉S
• 分子量: 781.903
• InChiKey: OBRKVXYHDPFRTL-UYVJAXBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  55
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  170
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  tert-butyl ((2R,3R)-4-(4-fluoro-N-methylphenylsulfonamido)-3-hydroxy-2-methylbutyl)((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)carbamate 在 2,6-二甲基吡啶 、 tin(II) chloride dihdyrate 、 四丁基氟化铵 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 二异丁基氢化铝 、 caesium carbonate 、 氟化氢吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 、 叔丁醇 为溶剂， 反应 134.0h， 生成 N-(((6R,7R)-12-(3-(3,5-dimethylisoxazol-4-yl)ureido)-9-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-7-methyl-10-oxo-2,3,4,6,7,8,9,10-octahydrobenzo[f][1,5,9]dioxaazacyclododecin-6-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

文献信息

• Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents
  作者：Eamon Comer、Jennifer A. Beaudoin、Nobutaka Kato、Mark E. Fitzgerald、Richard W. Heidebrecht、Maurice duPont Lee、Daniela Masi、Marion Mercier、Carol Mulrooney、Giovanni Muncipinto、Ann Rowley、Keila Crespo-Llado、Adelfa E. Serrano、Amanda K. Lukens、Roger C. Wiegand、Dyann F. Wirth、Michelle A. Palmer、Michael A. Foley、Benito Munoz、Christina A. Scherer、Jeremy R. Duvall、Stuart L. Schreiber

  DOI：10.1021/jm500994n

  日期：2014.10.23

  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.