N-(((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-11-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2,9-dimethyl-2,3,4,5,6,8,9,10,11,12-decahydrobenzo[b][1,9,5]dioxaazacyclotetradecin-8-yl)methyl)-4-fluoro-N-methylbenzenesulfonamide | 1403479-03-7

• 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: N-(((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-11-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2,9-dimethyl-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: N-(((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-11-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2,9-dimethyl-2,3,4,5,6,8,9,10,11,12-decahydrobenzo[b][1,9,5]dioxaazacyclotetradecin-8-yl)methyl)-4-fluoro-N-methylbenzenesulfonamide；1-(3,5-dimethyl-1,2-oxazol-4-yl)-3-[(3S,9R,10R)-9-[[(4-fluorophenyl)sulfonyl-methylamino]methyl]-12-[(2S)-1-[(4-methoxyphenyl)methoxy]propan-2-yl]-3,10-dimethyl-2,8-dioxa-12-azabicyclo[12.4.0]octadeca-1(14),15,17-trien-16-yl]urea
• CAS: 1403479-03-7
• 化学式: C₄₂H₅₆FN₅O₈S
• 分子量: 810.0
• InChiKey: SUHHEDOZELIJOX-GADYJKOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  57
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  N-(((2S,8R,9R)-14-amino-11-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-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 dimethyl sulfide borane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-(((2S,8R,9R)-14-(3-(3,5-dimethylisoxazol-4-yl)ureido)-11-((2S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2,9-dimethyl-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：

  [EN] MACROLACTAM COMPOUNDS AND METHODS FOR THE TREATMENT OF MALARIA
  [FR] COMPOSÉS MACROLACTAMES ET MÉTHODES DE TRAITEMENT DU PALUDISME

  摘要：

  公开号：

  WO2012142457A3

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
• 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.