tert-butyl ((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)carbamate | 1403480-40-9

• 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: tert-butyl ((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)carbamate
• 英文别名: tert-butyl ((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)carbamate
• CAS: 1403480-40-9
• 化学式: C₃₁H₄₅FN₂O₇S
• 分子量: 608.772
• InChiKey: WAIALWSTGGWUAO-UQARTHHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  42.0
• 可旋转键数：
  16.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  94.61
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl ((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)carbamate 在 2,6-二甲基吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium hydride 、 氟化氢吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 N-((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)-2-(2-(allyloxy)-5-nitrophenyl)-N-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)acetamide
  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：

  tert-butyl ((2R,3R)-3-((tert-butyldimethylsilyl)oxy)-4-(4-fluoro-N methylphenylsulfonamido)-2-methylbutyl)((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)carbamate 在 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 tert-butyl ((2R,3R)-3-(allyloxy)-4-(4-fluoro-N-methylphenylsulfonamido)-2-methylbutyl)((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)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

文献信息

• [EN] MACROLACTAM COMPOUNDS AND METHODS FOR THE TREATMENT OF MALARIA<br/>[FR] COMPOSÉS MACROLACTAMES ET MÉTHODES DE TRAITEMENT DU PALUDISME
  申请人：BROAD INST INC

  公开号：WO2012142457A3

  公开（公告）日：2013-02-07