2-[2-[[(1S)-1-benzyl-2-hydroxy-ethyl]amino]-2-oxo-ethoxy]-N,N-diethyl-6-fluoro-benzamide | 1224595-23-6

• 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: 2-[2-[[(1S)-1-benzyl-2-hydroxy-ethyl]amino]-2-oxo-ethoxy]-N,N-diethyl-6-fluoro-benzamide
• 英文别名: N,N-diethyl-2-fluoro-6-[2-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-2-oxoethoxy]benzamide
• CAS: 1224595-23-6
• 化学式: C₂₂H₂₇FN₂O₄
• 分子量: 402.466
• InChiKey: XPXBRIJIMYOJTM-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-2-fluoro-6-(2-((1-hydroxy-3-phenylpropan-2-yl)amino)-2-oxoethoxy)benzoic acid 、 二乙胺 在 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 2-[2-[[(1S)-1-benzyl-2-hydroxy-ethyl]amino]-2-oxo-ethoxy]-N,N-diethyl-6-fluoro-benzamide
  参考文献：
  名称：

  Inhibitors of hepatitis C virus polymerase: Synthesis and characterization of novel 2-oxy-6-fluoro-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-benzamides

  摘要：

  SAR exploration from an initial hit, (S)-N-(2-cyclohexenylethyl)-2-fluoro-6-(2-(1-hydroxy-3-phenylpropan-2-ylamino)-2-oxoethoxy)benzamide (1), identified using our proprietary automated ligand identification system (ALIS),(1) has led to a novel series of selective hepatitis C virus (HCV) NS5B polymerase inhibitors with improved in vitro potency as exemplified by (S)-2-fluoro-6-(2-(1-hydroxy-3-phenylpropan-2-ylamino)-2-oxoethoxy)-N-isopentyl-N-methylbenzamidecarboxamide (41) (IC(50) = 0.5 mu M). The crystal structure of an analogue (44) was solved and provided rationalization of the SAR of this series, which binds in a distinct manner in the palm domain of NS5B, consistent with biochemical analysis using enzyme mutant variants. These data warrant further lead optimization efforts on this novel series of non-nucleoside inhibitors targeting the HCV polymerase. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.054

文献信息

• Inhibitors of hepatitis C virus polymerase: Synthesis and characterization of novel 2-oxy-6-fluoro-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-benzamides
  作者：Cliff C. Cheng、Gerald W. Shipps、Zhiwei Yang、Noriyuki Kawahata、Charles A. Lesburg、José S. Duca、Jamie Bandouveres、Jack D. Bracken、Chuan-kui Jiang、Sony Agrawal、Eric Ferrari、H.-C. Huang

  DOI：10.1016/j.bmcl.2010.02.054

  日期：2010.4

  SAR exploration from an initial hit, (S)-N-(2-cyclohexenylethyl)-2-fluoro-6-(2-(1-hydroxy-3-phenylpropan-2-ylamino)-2-oxoethoxy)benzamide (1), identified using our proprietary automated ligand identification system (ALIS),(1) has led to a novel series of selective hepatitis C virus (HCV) NS5B polymerase inhibitors with improved in vitro potency as exemplified by (S)-2-fluoro-6-(2-(1-hydroxy-3-phenylpropan-2-ylamino)-2-oxoethoxy)-N-isopentyl-N-methylbenzamidecarboxamide (41) (IC(50) = 0.5 mu M). The crystal structure of an analogue (44) was solved and provided rationalization of the SAR of this series, which binds in a distinct manner in the palm domain of NS5B, consistent with biochemical analysis using enzyme mutant variants. These data warrant further lead optimization efforts on this novel series of non-nucleoside inhibitors targeting the HCV polymerase. (C) 2010 Elsevier Ltd. All rights reserved.