(2S)-2-[(2S,8R,9R)-2,9-dimethyl-8-[(N-methyl(4-fluorobenzene)sulfonamido)methyl]-12-oxo-14-[(phenylcarbamoyl)amino]-2,3,4,5,6,8,9,10,11,12-decahydro-1,7,11-benzodioxaazacyclotetradecin-11-yl]propyl 2,2-dimethylpropanoate | 1353557-48-8

• 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: (2S)-2-[(2S,8R,9R)-2,9-dimethyl-8-[(N-methyl(4-fluorobenzene)sulfonamido)methyl]-12-oxo-14-[(phenylcarbamoyl)amino]-2,3,4,5,6,8,9,10,11,12-decahydro-1,7,11-benzodioxaazacyclotetradecin-11-yl]propyl 2,2-dimethylpropanoate
• 英文别名: (2S)-2-[(2S,8R,9R)-2,9-dimethyl-8-{[N-methyl(4-fluorobenzene)sulfonamido]methyl}-12-oxo-14-[(phenylcarbamoyl)amino]-2,3,4,5,6,8,9,10,11,12-decahydro-1,7,11-benzodioxazacyclotetradecin-11-yl]propyl 2,2-dimethylpropanoate；2,2-dimethylpropanoic acid [(2S)-2-[(3S,9R,10R)-16-[[anilino(oxo)methyl]amino]-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-12-yl]propyl] ester；[(2S)-2-[(3S,9R,10R)-9-[[(4-fluorophenyl)sulfonyl-methylamino]methyl]-3,10-dimethyl-13-oxo-16-(phenylcarbamoylamino)-2,8-dioxa-12-azabicyclo[12.4.0]octadeca-1(14),15,17-trien-12-yl]propyl] 2,2-dimethylpropanoate
• CAS: 1353557-48-8
• 化学式: C₄₀H₅₃FN₄O₈S
• 分子量: 768.947
• InChiKey: JYLJYHDOXFQHEK-WVEXKQSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  54
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  1-((2S,8R,9R)-11-((S)-1-((4-methoxybenzyl)oxy)propan-2-yl)-2,9-dimethyl-8-((methylamino)methyl)-12-oxo-3,4,5,6,9,10,11,12-octahydro-2H,8H-benzo[b][1,9]dioxa[5]azacyclotetradecin-14-yl)-3-phenylurea 在 吡啶 、 2,6-二甲基吡啶 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 31.0h， 生成 (2S)-2-[(2S,8R,9R)-2,9-dimethyl-8-[(N-methyl(4-fluorobenzene)sulfonamido)methyl]-12-oxo-14-[(phenylcarbamoyl)amino]-2,3,4,5,6,8,9,10,11,12-decahydro-1,7,11-benzodioxaazacyclotetradecin-11-yl]propyl 2,2-dimethylpropanoate
  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 Yields a Novel Lead for the Treatment of Malaria
  作者：Richard W. Heidebrecht、Carol Mulrooney、Christopher P. Austin、Robert H. Barker、Jennifer A. Beaudoin、Ken Chih-Chien Cheng、Eamon Comer、Sivaraman Dandapani、Justin Dick、Jeremy R. Duvall、Eric H. Ekland、David A. Fidock、Mark E. Fitzgerald、Michael Foley、Rajarshi Guha、Paul Hinkson、Martin Kramer、Amanda K. Lukens、Daniela Masi、Lisa A. Marcaurelle、Xin-Zhuan Su、Craig J. Thomas、Michel Weïwer、Roger C. Wiegand、Dyann Wirth、Menghang Xia、Jing Yuan、Jinghua Zhao、Michelle Palmer、Benito Munoz、Stuart Schreiber

  DOI：10.1021/ml200244k

  日期：2012.2.9

  Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238.