(2S,3S)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methylpropanoic acid | 376584-66-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (2S,3S)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methylpropanoic acid
• CAS: 376584-66-6
• 化学式: C₁₀H₁₀Cl₂O₃
• 分子量: 249.094
• InChiKey: KQCLTECEQACQPU-CDUCUWFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-3-amino-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one 、 (2S,3S)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methylpropanoic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 乙腈 为溶剂， 生成 (2S,3S)-3-(3,4-Dichlorophenyl)-3-hydroxy-2-methyl-N-((3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-propionamide
  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：

  (4R)-4-benzyl-3-[(2S,3S)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methylpropanoyl]-1,3-oxazolidin-2-one 在 lithium hydroxide 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,3S)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methylpropanoic acid
  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.