3-甲基-3H-苯并[D][1,2]二氮杂-4(5H)-酮 | 400819-99-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 3-甲基-3H-苯并[D][1,2]二氮杂-4(5H)-酮
• 英文名称: 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one
• 英文别名: 3-methyl-3H-benzo[d][1,2]diazepin-4(5H)-one；3-methyl-5H-2,3-benzodiazepin-4-one
• CAS: 400819-99-0
• 化学式: C₁₀H₁₀N₂O
• 分子量: 174.202
• InChiKey: FTLQNFDLQJSQKY-UHFFFAOYSA-N

物化性质

• 沸点：
  303.5±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-甲基-3H-苯并[D][1,2]二氮杂-4(5H)-酮 在 palladium on activated charcoal 2,4,6-三异丙基苯磺酰叠氮化物 、 氢气 、 氯甲酸乙酯 、 双(三甲基硅烷基)氨基钾 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 5.67h， 生成 (2S)-2-amino-4-methyl-N-(3-methyl-4-oxo-5H-2,3-benzodiazepin-5-yl)pentanamide
  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：

  2-(2-甲酰基苯基)乙酸 以 乙醇 为溶剂， 反应 2.0h， 生成 3-甲基-3H-苯并[D][1,2]二氮杂-4(5H)-酮
  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

文献信息

• Tetrazolylpropionamides as inhibitors of Abeta protein production
  申请人：——

  公开号：US20040082568A1

  公开（公告）日：2004-04-29

  This invention relates to novel tetrazolylpropionamides in which the amide group comprises an aminoazepinone, and related structures, of Formula (I): 1 or pharmaceutically acceptable salt or prodrug forms thereof, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A&bgr;-peptide, thereby resulting in prevention and treatment of the neuropathology associated with production of A&bgr;-peptide. More particularly, the present invention relates to the treatment of neurological disorders related to &bgr;-amyloid production such as Alzheimer's disease.

  这项发明涉及新型四唑基丙酰胺，其中酰胺基团包括氨基环庚酮，以及与之相关的结构，化学式（I）： 1 或其药学上可接受的盐或前药形式，它们的药物组合物和使用方法。这些新型化合物抑制淀粉样前体蛋白的加工，更具体地说，抑制Aβ-肽的产生，从而预防和治疗与Aβ-肽产生相关的神经病理学。更具体地，本发明涉及与β-淀粉样蛋白产生相关的神经系统疾病的治疗，如阿尔茨海默病。
• 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的定义如本文所述，这些衍生物是β-淀粉样肽（β-AP）生产的抑制剂，可用于治疗阿尔茨海默病和其他因淀粉样物质在细胞中异常沉积而引起的疾病。
• Benzodiazepinone &bgr;-amyloid inhibitors: arylacetamidoalanyl derivatives
  申请人：Bristol-Myers Squibb Company

  公开号：US06432944B1

  公开（公告）日：2002-08-13

  There is provided a series of arylacetamidoalanyl derivatives of benzodiazepinones of Formula I wherein R1 through R7 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。
• Tetrazolylpropionamides as inhibitors of Aβ protein production
  申请人：Bristol-Myers Squibb Company

  公开号：US07001901B2

  公开（公告）日：2006-02-21

  This invention relates to novel tetrazolyl-propionamides in which the amide group comprises an aminoazepinone, and related structures, of Formula (I): or pharmaceutically acceptable salt or prodrug forms thereof, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby resulting in prevention and treatment of the neuropathology associated with production of Aβ-peptide. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer's disease.

  本发明涉及一种新型四唑基丙酰胺，其中酰胺基包括一种氨基环己酮，以及相关结构，化学式（I）或其药学上可接受的盐或前药形式，它们的药物组合物和使用方法。这些新化合物抑制淀粉样前体蛋白的处理，更具体地说，抑制Aβ肽的产生，从而预防和治疗与Aβ肽产生相关的神经病理学。更具体地，本发明涉及与β-淀粉样蛋白产生相关的神经系统疾病的治疗，如阿尔茨海默病。
• US6432944B1
  申请人：——

  公开号：US6432944B1

  公开（公告）日：2002-08-13