(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 | 564462-34-6

• 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)-4-hydroxy-N-[(3S)1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4benzodiazepin-3-yl]butanamide
• 英文别名: (2S,3R)-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]butanamide
• CAS: 564462-34-6
• 化学式: C₃₂H₂₆F₃N₃O₃
• 分子量: 557.572
• InChiKey: UQVZOXIXMAJWBW-PDVBFRJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  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：
  0.16
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (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 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 生成 (2S,3R)-4-bromo-3-(3,4-difluorophenyl)-2-(4-fluorophenyl)-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-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 在 1-羟基苯并三唑 、 臭氧 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 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

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。
• [EN] BENZODIAZEPINE DERIVATIVES AS APP MODULATORS<br/>[FR] DERIVES DE BENZODIAZEPINE UTILISES COMME MODULATEURS DE LA PROTEINE PRECURSEUR AMYLOIDE (APP)
  申请人：MERCK SHARP & DOHME

  公开号：WO2001090084A1

  公开（公告）日：2001-11-29

  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 η-secretase, and hence find use in the treatment or prevention of conditions associated with the deposition of β-amyloid, such as Alzheimer's disease.

  一种新型的1,4-和1,5-苯二氮平类化合物的式(I)被揭示。这些化合物通过调节η-分泌酶对淀粉样前体蛋白的加工，因此可用于治疗或预防与β-淀粉样蛋白沉积有关的疾病，如阿尔茨海默病。
• CYCLOBUTYL SULFONES AS NOTCH SPARING GAMMA SECRETASE INHIBITORS
  申请人：Heidebrecht Richard W.

  公开号：US20110039925A1

  公开（公告）日：2011-02-17

  The invention encompasses a novel class of cyclobutyl sulfone derivatives which inhibit the processing of APP by the putative γ-secretase while sparing Notch signaling pathway, and thus are useful in the treatment or prevention of Alzheimer's disease without the development of Notch inhibition mediated gastrointestinal issues. Pharmaceutical compositions and methods of use are also included.

  该发明涵盖了一种新型环丁基磺酰衍生物类，其抑制假定的γ-分泌酶对APP的加工，同时保留Notch信号通路，因此可用于治疗或预防阿尔茨海默病，而不会引起Notch抑制介导的胃肠问题。此外，还包括药物组合物和使用方法。
• BENZODIAZEPINE DERIVATIVES AS APP MODULATORS
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1294702A1

  公开（公告）日：2003-03-26
• US7105509B2
  申请人：——

  公开号：US7105509B2

  公开（公告）日：2006-09-12