(2R, 3R)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methyl-N-((3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)-propionamide | 376581-96-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R, 3R)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methyl-N-((3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)-propionamide
• 英文别名: (2R,3R)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methyl-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]propanamide
• CAS: 376581-96-3
• 化学式: C₂₆H₂₃Cl₂N₃O₃
• 分子量: 496.393
• InChiKey: MDNYRQJCZQDXBV-ZYNUUPFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R, 3R)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methyl-N-((3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)-propionamide 在 吡啶 、 盐酸羟胺 、 戴斯-马丁氧化剂 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 (3E)-3-(3,4-dichlorophenyl)-3-(hydroxyimino)-2-methyl-N-[(3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3yl]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：

  (4R)-4-benzyl-3-[(2R,3R)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methylpropanoyl]-1,3-oxazolidin-2-one 在 lithium hydroxide 、 双氧水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 (2R, 3R)-3-(3,4-dichlorophenyl)-3-hydroxy-2-methyl-N-((3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-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

文献信息

• Benzodiazepine derivatives as app modulators
  申请人：——

  公开号：US20040082572A1

  公开（公告）日：2004-04-29

  A novel class of 1,4- and 1,5-benzodiazepines of formula (I) is disclosed. The compounds modulate the processing of amyloid precursor protein by &ggr;-secretase, and hence find use in the treatment or prevention of conditions associated with the deposition of &bgr;-amyloid, such as Alzheimer's disease. 1

  公开了一种式(I)的新型1,4-和1,5-苯二氮平类化合物。这些化合物调节&ggr;-分泌酶对淀粉样前体蛋白的加工作用，因此可用于治疗或预防与&bgr;-淀粉样蛋白沉积相关的疾病，如阿尔茨海默病。