4-fluoro-N-(((6S,12R,13R)-15-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-6,13-dimethyl-16-oxo-6,7,8,9,10,12,13,14,15,16-decahydropyrido[3,2-b][1,9,5]dioxaazacyclotetradecin-12-yl)methyl)-N-methylbenzenesulfonamide | 1403478-94-3

• 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: 4-fluoro-N-(((6S,12R,13R)-15-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-6,13-dimethyl-16-oxo-6,7,8,9,10,12,13,14,15,16-decahydropyrido[3,2-b][1,9,5]dioxaazacyclotetradecin-12-yl)methyl)-N-methylbenzenesulfonamide
• 英文别名: 4-fluoro-N-{[(6S,12R,13R)-15-[(2S)-1-[(4-methoxyphenyl)methoxy]propan-2-yl]-6,13-dimethyl-16-oxo-6H,7H,8H,9H,10H,12H,13H,14H,15H,16H-pyrido[3,2-b]1,9-dioxa-5-azacyclotetradecan-12-yl]methyl}-N-methylbenzene-1-sulfonamide；4-fluoro-N-[[(3S,9R,10R)-12-[(2S)-1-[(4-methoxyphenyl)methoxy]propan-2-yl]-3,10-dimethyl-13-oxo-2,8-dioxa-12,15-diazabicyclo[12.4.0]octadeca-1(14),15,17-trien-9-yl]methyl]-N-methylbenzenesulfonamide
• CAS: 1403478-94-3
• 化学式: C₃₅H₄₆FN₃O₇S
• 分子量: 671.831
• InChiKey: HZKRPZDBEGUAAG-XJVVAVADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  tert-butyl ((2R,3S)-2-((tert-butyldimethylsilyl)oxy)-4-(((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)amino)-3-methyl-4-oxobutyl)(methyl)carbamate 在 2,6-二甲基吡啶 、 Hoveyda-Grubbs catalyst second generation 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 sodium hydride 、 氟化氢吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 生成 4-fluoro-N-(((6S,12R,13R)-15-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-6,13-dimethyl-16-oxo-6,7,8,9,10,12,13,14,15,16-decahydropyrido[3,2-b][1,9,5]dioxaazacyclotetradecin-12-yl)methyl)-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.