5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-((methylsulfonyl){(2R)-3-[(phenylmethyl)oxy]-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]propyl}amino)-1-benzofuran-3-carboxamide | 1378433-27-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 2-芳基苯并呋喃类黄酮
• 英文名称: 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-((methylsulfonyl){(2R)-3-[(phenylmethyl)oxy]-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]propyl}amino)-1-benzofuran-3-carboxamide
• 英文别名: 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-[methylsulfonyl-[(2R)-2-(phenylmethoxymethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]amino]-1-benzofuran-3-carboxamide
• CAS: 1378433-27-2
• 化学式: C₃₇H₄₄BFN₂O₇S
• 分子量: 690.641
• InChiKey: WGKMLFIMTQDWES-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.17
• 重原子数：
  49
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-((methylsulfonyl){(2R)-3-[(phenylmethyl)oxy]-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]propyl}amino)-1-benzofuran-3-carboxamide 在 palladium 10% on activated carbon 氢气 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 18.0h， 以68.3%的产率得到5-cyclopropyl-2-(4-fluorophenyl)-6-[{[(4R)-2-hydroxy-1,2-oxaborolan-4 yl]methyl}(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  本发明涉及式(I)的化合物及其盐，包括所述化合物的药物组合物，以及利用这些化合物治疗或预防病毒感染，如HCV感染，以及与此类感染相关的疾病。

  公开号：

  WO2012067663A1
• 作为产物：
  描述：

  (4R,5S)-4-methyl-5-phenyl-3-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanoyl]-1,3-oxazolidin-2-one 在 锂硼氢 、 偶氮二甲酸二异丙酯 、 四氯化钛 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 18.17h， 生成 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-((methylsulfonyl){(2R)-3-[(phenylmethyl)oxy]-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]propyl}amino)-1-benzofuran-3-carboxamide
  参考文献：
  名称：

  Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase

  摘要：

  A boronic acid moiety was found to be a critical pharmacophore for enhanced in vitro potency against wild-type hepatitis C replicons and known clinical polymorphic and resistant HCV mutant replicons. The synthesis, optimization, and structure-activity relationships associated with inhibition of HCV replication in a subgenomic replication system for a series of non-nucleoside boron-containing HCV RNA-dependent RNA polymerase (NS5B) inhibitors are described. A summary of the discovery of 3 (GSK5852), a molecule which entered clinical trials in subjects infected with HCV in 2011, is included.

  DOI：

  10.1021/jm400317w

文献信息

• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2012067663A1

  公开（公告）日：2012-05-24

  The present invention features compounds of formula (I): and salts thereof, pharmaceutical compositions comprising said compounds, and uses of such compounds in treating or preventing viral infections, such as HCV infections, and diseases associated with such infections.

  本发明涉及式(I)的化合物及其盐，包括所述化合物的药物组合物，以及利用这些化合物治疗或预防病毒感染，如HCV感染，以及与此类感染相关的疾病。
• Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase
  作者：Andrew Maynard、Renae M. Crosby、Byron Ellis、Robert Hamatake、Zhi Hong、Brian A. Johns、Kirsten M. Kahler、Cecilia Koble、Anna Leivers、Martin R. Leivers、Amanda Mathis、Andrew J. Peat、Jeffrey J. Pouliot、Christopher D. Roberts、Vicente Samano、Rachel M. Schmidt、Gary K. Smith、Andrew Spaltenstein、Eugene L. Stewart、Pia Thommes、Elizabeth M. Turner、Christian Voitenleitner、Jill T. Walker、Greg Waitt、Jason Weatherhead、Kurt Weaver、Shawn Williams、Lois Wright、Zhiping Z. Xiong、David Haigh、J. Brad Shotwell

  DOI：10.1021/jm400317w

  日期：2014.3.13

  A boronic acid moiety was found to be a critical pharmacophore for enhanced in vitro potency against wild-type hepatitis C replicons and known clinical polymorphic and resistant HCV mutant replicons. The synthesis, optimization, and structure-activity relationships associated with inhibition of HCV replication in a subgenomic replication system for a series of non-nucleoside boron-containing HCV RNA-dependent RNA polymerase (NS5B) inhibitors are described. A summary of the discovery of 3 (GSK5852), a molecule which entered clinical trials in subjects infected with HCV in 2011, is included.