(R)-3-(benzyloxy)-2-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)propan-1-ol | 1378433-26-1

• 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: (R)-3-(benzyloxy)-2-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)propan-1-ol
• 英文别名: (2R)-2-(phenylmethoxymethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-ol
• CAS: 1378433-26-1
• 化学式: C₁₇H₂₇BO₄
• 分子量: 306.21
• InChiKey: XSJIBEAYNRFKIL-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-环丙基-2-(4-氟苯基)-N-甲基-6-(甲基磺酰氨基)苯并呋喃-3-甲酰胺 、 (R)-3-(benzyloxy)-2-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)propan-1-ol 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以78%的产率得到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
• 作为产物：
  描述：

  联硼酸频那醇酯 在 锂硼氢 、 四氯化钛 、 双(2-二苯基磷苯基)醚 、 copper(l) chloride 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 5.92h， 生成 (R)-3-(benzyloxy)-2-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)propan-1-ol
  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

• 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.