N-(((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-2,9-dimethyl-11-((2S)-1-morpholinopropan-2-yl)-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

• 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)-2,9-dimethyl-11-((2S)-1-morpholinopropan-2-yl)-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-12-[(2S)-1-morpholin-4-ylpropan-2-yl]-13-oxo-2,8-dioxa-12-azabicyclo[12.4.0]octadeca-1(14),15,17-trien-16-yl]urea
• 化学式: C₃₈H₅₃FN₆O₈S
• 分子量: 772.939
• InChiKey: DDMCICAERZKXBA-PUNARZIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  54
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  164
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  、 二氯乙醚 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以13%的产率得到N-(((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-2,9-dimethyl-11-((2S)-1-morpholinopropan-2-yl)-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

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.