5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1 1-dimethylethyl ester | 400819-97-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1 1-dimethylethyl ester
• 英文别名: tert-butyl 5-azido-3-methyl-4-oxo-1,5-dihydro-2,3-benzodiazepine-2-carboxylate
• CAS: 400819-97-8
• 化学式: C₁₅H₁₉N₅O₃
• 分子量: 317.348
• InChiKey: YTTCVQJEGHMSBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  64.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1 1-dimethylethyl ester 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.67h， 生成 tert-butyl 5-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-3-methyl-4-oxo-1,3,4,5-tetrahydro-2H-benzo[d][1,2]diazepine-2-carboxylate
  参考文献：
  名称：

  Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796): A γ-secretase inhibitor with Aβ lowering activity in a transgenic mouse model of Alzheimer’s disease

  摘要：

  We report on the design of benzodiazepin ones as peptidomimetics at the carboxy terminus of hydroxyamides. structure-activity relationships of diazepinones were investigated and orally active gamma-secretase inhibitors were synthesized. Active metabolites contributing to AP reduction were identified by analysis of plasma samples from Tg2576 mice. In particular, (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796) was identified with an acceptable pharmacodynamic and pharmacokinetic profile. Chronic dosing of BMS-433796 in Tg2576 mice suggested a narrow therapeutic window and Notch-mediated toxicity at higher doses. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.082
• 作为产物：
  描述：

  1-Boc-2-甲基肼 在 偶氮二甲酸二异丙酯 、 2,4,6-三异丙基苯磺酰叠氮化物 、 双(三甲基硅烷基)氨基钾 、 溶剂黄146 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1 1-dimethylethyl ester
  参考文献：
  名称：

  Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796): A γ-secretase inhibitor with Aβ lowering activity in a transgenic mouse model of Alzheimer’s disease

  摘要：

  We report on the design of benzodiazepin ones as peptidomimetics at the carboxy terminus of hydroxyamides. structure-activity relationships of diazepinones were investigated and orally active gamma-secretase inhibitors were synthesized. Active metabolites contributing to AP reduction were identified by analysis of plasma samples from Tg2576 mice. In particular, (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796) was identified with an acceptable pharmacodynamic and pharmacokinetic profile. Chronic dosing of BMS-433796 in Tg2576 mice suggested a narrow therapeutic window and Notch-mediated toxicity at higher doses. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.082
• 作为试剂：
  描述：

  2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1,1-dimethylethyl ester 、 双(三甲基硅烷基)氨基钾 、 甲苯 、 2,4,6-三异丙基苯磺酰叠氮化物 、 、 溶剂黄146 在 水 、 碳酸氢钠 、 盐酸 、 Brine 、 5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1 1-dimethylethyl ester 、 silica 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 6.35h， 以The azide was obtained in 60% yield的产率得到5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1 1-dimethylethyl ester
  参考文献：
  名称：

  Benzodiazepinone &bgr;-amyloid inhibitors: arylacetamidoalanyl derivatives

  摘要：

  提供了一系列苯二氮平酮的芳基乙酰胺基丙氨酸衍生物，其化学式为I，其中R1至R7和n的定义见此处，它们是β-淀粉样肽（β-AP）产生的抑制剂，可用于治疗阿尔茨海默病和其他表现为淀粉样物质异常沉积的疾病。

  公开号：

  US06432944B1

文献信息

• Benzodiazepinone beta -amyloid inhibitors: arylacetamidoalanyl derivatives
  申请人：——

  公开号：US20020022621A1

  公开（公告）日：2002-02-21

  There is provided a series of arylacetamidoalanyl derivatives of benzodiazepinones of Formula I 1 wherein R 1 through R 7 and n are defined herein, which are inhibitors of &bgr;-amyloid peptide (&bgr;-AP) production and are useful in the treatment of Alzheimer's Disease and other conditions characterized by aberrant extract cellular deposition of amyloid.

  提供了一系列苯二氮平酮的芳基乙酰胺基丙氨酸衍生物，其化学式为I1，其中R1至R7和n的定义如下，它们是β-淀粉样肽（β-AP）生产的抑制剂，并且在治疗阿尔茨海默病和其他以淀粉样物质异常沉积为特征的疾病中有用。