N-(((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-11-isopropyl-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 | 1403478-99-8

• 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)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-11-isopropyl-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: 1-(3,5-dimethyl-1,2-oxazol-4-yl)-3-[(3S,9R,10R)-9-[[(4-fluorophenyl)sulfonyl-methylamino]methyl]-3,10-dimethyl-13-oxo-12-propan-2-yl-2,8-dioxa-12-azabicyclo[12.4.0]octadeca-1(14),15,17-trien-16-yl]urea
• CAS: 1403478-99-8
• 化学式: C₃₄H₄₆FN₅O₇S
• 分子量: 687.833
• InChiKey: WQBJNAABSRHKMK-UDKTZTBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  48
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  tert-butyl ((2R,3R)-2-((tert-butyldimethylsilyl)oxy)-4-(isopropylamino)-3-methylbutyl)(methyl)carbamate 在 2,6-二甲基吡啶 、 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 、 palladium(II) hydroxide 、 sodium hydride 、 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 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 130.5h， 生成 N-(((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-11-isopropyl-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
  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