(2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]pent-4-enamide | 376584-21-3

• 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-difluorophenyl)-2-(4-fluorophenyl)-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]pent-4-enamide
• CAS: 376584-21-3
• 化学式: C₃₃H₂₆F₃N₃O₂
• 分子量: 553.584
• InChiKey: NFBNZYBJQBPIFN-QLZDYINWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  61.8
• 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-difluorophenyl)-2-(4-fluorophenyl)-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]pent-4-enamide 在 臭氧 、 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-[(3S)1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4benzodiazepin-3-yl]butanamide
  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：

  (S)-3-amino-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one 、 (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)pent-4-enoic acid 在 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 二氯甲烷 为溶剂， 生成 (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]pent-4-enamide
  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。
• US7105509B2
  申请人：——

  公开号：US7105509B2

  公开（公告）日：2006-09-12