N-(((2S,8R,9R)-11-((2S)-1-(dimethylamino)propan-2-yl)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-2,9-dimethyl-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 | 1403479-42-4

• 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-(((2S,8R,9R)-11-((2S)-1-(dimethylamino)propan-2-yl)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-2,9-dimethyl-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
• 英文别名: 3-(dimethyl-1,2-oxazol-4-yl)-1-[(2S,8R,9R)-11-[(2S)-1-(dimethylamino)propan-2-yl]-2,9-dimethyl-8-{[N-methyl(4-fluorobenzene)sulfonamido]methyl}-12-oxo-2,3,4,5,6,8,9,10,11,12-decahydro-1,7,11-benzodioxazacyclotetradecin-14-yl]urea；1-[(3S,9R,10R)-12-[(2S)-1-(dimethylamino)propan-2-yl]-9-[[(4-fluorophenyl)sulfonyl-methylamino]methyl]-3,10-dimethyl-13-oxo-2,8-dioxa-12-azabicyclo[12.4.0]octadeca-1(14),15,17-trien-16-yl]-3-(3,5-dimethyl-1,2-oxazol-4-yl)urea
• CAS: 1403479-42-4
• 化学式: C₃₆H₅₁FN₆O₇S
• 分子量: 730.901
• InChiKey: YZWMPMDITONCIO-DWYUEALBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  51
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-(((2S,8R,9R)-11-((2S)-1-(dimethylamino)propan-2-yl)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-2,9-dimethyl-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 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以35.8%的产率得到(S)-2-((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-8-((4-fluoro-N-methylphenylsulfonamido)methyl)-2,9-dimethyl-12-oxo-3,4,5,6,9,10-hexahydrobenzo[b][1,9,5]dioxaazacyclotetradecin-11(2H,8H,12H)-yl)-N,N-dimethylpropan-1-amine oxide
  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