(4R)-4-benzyl-3-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-3-(3,4-dichlorophenyl)-2-(4-fluorophenyl)propanoyl]-1,3-oxazolidin-2-one | 1025928-40-8

• 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: (4R)-4-benzyl-3-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-3-(3,4-dichlorophenyl)-2-(4-fluorophenyl)propanoyl]-1,3-oxazolidin-2-one
• CAS: 1025928-40-8
• 化学式: C₃₁H₃₄Cl₂FNO₄Si
• 分子量: 602.605
• InChiKey: ABDMRHHSPQKZHO-RTVRTQBESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.57
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R)-4-benzyl-3-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-3-(3,4-dichlorophenyl)-2-(4-fluorophenyl)propanoyl]-1,3-oxazolidin-2-one 在 lithium hydroxide 、 四丁基氟化铵 、 双氧水 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2R,3R)-3-(3,4-dichlorophenyl)-2-(4-fluorophenyl)-3-hydroxy-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]propanamide
  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：

  对氟苯乙酰氯 在 2,6-二甲基吡啶 、 正丁基锂 、 三氟甲磺酸二丁硼 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (4R)-4-benzyl-3-[(2R,3R)-3-[tert-butyl(dimethyl)silyl]oxy-3-(3,4-dichlorophenyl)-2-(4-fluorophenyl)propanoyl]-1,3-oxazolidin-2-one
  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