(S)-2-fluoro-6-(2-((1-hydroxy-3-phenylpropan-2-yl)amino)-2-oxoethoxy)benzoic acid | 1224594-85-7

• 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: (S)-2-fluoro-6-(2-((1-hydroxy-3-phenylpropan-2-yl)amino)-2-oxoethoxy)benzoic acid
• CAS: 1224594-85-7
• 化学式: C₁₈H₁₈FNO₅
• 分子量: 347.343
• InChiKey: TWGCWLCRLURFSN-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.62
• 重原子数：
  25.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  95.86
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  甲基丁胺 、 (S)-2-fluoro-6-(2-((1-hydroxy-3-phenylpropan-2-yl)amino)-2-oxoethoxy)benzoic acid 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-hydroxyethyl]amino}-2-oxoethoxy)-N-butyl-6-fluoro-N-methylbenzamide
  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
• 作为产物：
  描述：

  methyl (S)-2-fluoro-6-(2-((1-hydroxy-3-phenylpropan-2-yl)amino)-2-oxoethoxy)benzoate 在 sodium hydroxide 、 盐酸 、 水 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 生成 (S)-2-fluoro-6-(2-((1-hydroxy-3-phenylpropan-2-yl)amino)-2-oxoethoxy)benzoic acid
  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