(2S,3R)-3-(3,4-Difluoro-phenyl)-2-(4-fluoro-phenyl)-5-hydroxy-pentanoic acid benzyl ester | 1027923-77-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (2S,3R)-3-(3,4-Difluoro-phenyl)-2-(4-fluoro-phenyl)-5-hydroxy-pentanoic acid benzyl ester
• 英文别名: benzyl (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-5-hydroxypentanoate
• CAS: 1027923-77-8
• 化学式: C₂₄H₂₁F₃O₃
• 分子量: 414.424
• InChiKey: CWWZAOLOJPJFKP-NZQKXSOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3R)-3-(3,4-Difluoro-phenyl)-2-(4-fluoro-phenyl)-5-hydroxy-pentanoic acid benzyl ester 在 palladium on activated charcoal 2,6-二甲基吡啶 、 四丁基氟化铵 、 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -78.0~40.0 ℃ 、275.79 kPa 条件下， 生成 3-(3,4-difluoro-phenyl)-2-(4-fluoro-phenyl)-5-hydroxy-pentanoic acid (2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide
  参考文献：
  名称：

  Design and Synthesis of Highly Potent Benzodiazepine γ-Secretase Inhibitors:  Preparation of (2S,3R)-3-(3,4- Difluorophenyl)-2-(4-fluorophenyl)-4- hydroxy-N-((3S)-1-methyl-2-oxo-5- phenyl-2,3-dihydro-1H-benzo[e][1,4]- diazepin-3-yl)butyramide by Use of an Asymmetric Ireland−Claisen Rearrangement

  摘要：

  Novel benzodiazepine-containing gamma-secretase inhibitors for potential use in Alzheimer's disease have been designed that incorporate a substituted hydrocinnamide C-3 side chain. A syn combination of alpha-alkyl or aryl and beta-hydroxy or hydroxymethyl substituents was shown to give highly potent compounds. In particular, (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyramide (34) demonstrated excellent in vitro potency (IC50 = 0.06nM). 34 could also be selectively methylated to give [H-3]-28, which is of use in radioligand binding assays.

  DOI：

  10.1021/jm034058a
• 作为产物：
  描述：

  (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)pent-4-enoic acid 在 硼烷四氢呋喃络合物 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,3R)-3-(3,4-Difluoro-phenyl)-2-(4-fluoro-phenyl)-5-hydroxy-pentanoic acid benzyl ester
  参考文献：
  名称：

  Design and Synthesis of Highly Potent Benzodiazepine γ-Secretase Inhibitors:  Preparation of (2S,3R)-3-(3,4- Difluorophenyl)-2-(4-fluorophenyl)-4- hydroxy-N-((3S)-1-methyl-2-oxo-5- phenyl-2,3-dihydro-1H-benzo[e][1,4]- diazepin-3-yl)butyramide by Use of an Asymmetric Ireland−Claisen Rearrangement

  摘要：

  Novel benzodiazepine-containing gamma-secretase inhibitors for potential use in Alzheimer's disease have been designed that incorporate a substituted hydrocinnamide C-3 side chain. A syn combination of alpha-alkyl or aryl and beta-hydroxy or hydroxymethyl substituents was shown to give highly potent compounds. In particular, (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyramide (34) demonstrated excellent in vitro potency (IC50 = 0.06nM). 34 could also be selectively methylated to give [H-3]-28, which is of use in radioligand binding assays.

  DOI：

  10.1021/jm034058a

文献信息

• Design and Synthesis of Highly Potent Benzodiazepine γ-Secretase Inhibitors:  Preparation of (2<i>S</i>,3<i>R</i>)-3-(3,4- Difluorophenyl)-2-(4-fluorophenyl)-4- hydroxy-<i>N</i>-((3<i>S</i>)-1-methyl-2-oxo-5- phenyl-2,3-dihydro-1<i>H</i>-benzo[<i>e</i>][1,4]- diazepin-3-yl)butyramide by Use of an Asymmetric Ireland−Claisen Rearrangement
  作者：Ian Churcher、Susie Williams、Sonia Kerrad、Timothy Harrison、José L. Castro、Mark S. Shearman、Huw D. Lewis、Earl E. Clarke、Jonathan D. J. Wrigley、Dirk Beher、Yui S. Tang、Wensheng Liu

  DOI：10.1021/jm034058a

  日期：2003.6.1

  Novel benzodiazepine-containing gamma-secretase inhibitors for potential use in Alzheimer's disease have been designed that incorporate a substituted hydrocinnamide C-3 side chain. A syn combination of alpha-alkyl or aryl and beta-hydroxy or hydroxymethyl substituents was shown to give highly potent compounds. In particular, (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyramide (34) demonstrated excellent in vitro potency (IC50 = 0.06nM). 34 could also be selectively methylated to give [H-3]-28, which is of use in radioligand binding assays.