2-[2-[2-(Hydroxymethyl)phenyl]-1-oxoethyl]-2-methylhydrazinecarboxylic acid, 1,1-dimethylethyl ester | 400819-95-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[2-[2-(Hydroxymethyl)phenyl]-1-oxoethyl]-2-methylhydrazinecarboxylic acid, 1,1-dimethylethyl ester
• 英文别名: tert-butyl N-[[2-[2-(hydroxymethyl)phenyl]acetyl]-methylamino]carbamate
• CAS: 400819-95-6
• 化学式: C₁₅H₂₂N₂O₄
• 分子量: 294.351
• InChiKey: LODUVVLEWCPNGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[2-[2-(Hydroxymethyl)phenyl]-1-oxoethyl]-2-methylhydrazinecarboxylic acid, 1,1-dimethylethyl ester 在 palladium on activated charcoal 偶氮二甲酸二异丙酯 、 2,4,6-三异丙基苯磺酰叠氮化物 、 氢气 、 双(三甲基硅烷基)氨基钾 、 三苯基膦 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 12.67h， 生成 tert-butyl 5-amino-3-methyl-4-oxo-1,5-dihydro-2,3-benzodiazepine-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：

  3-异色酮 、 1-Boc-2-甲基肼 以 正己烷 、 溶剂黄146 、 乙酸乙酯 为溶剂， 生成 2-[2-[2-(Hydroxymethyl)phenyl]-1-oxoethyl]-2-methylhydrazinecarboxylic acid, 1,1-dimethylethyl ester
  参考文献：
  名称：

  Benzodiazepinone beta -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。

  公开号：

  US20020022621A1

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。
• 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
  作者：C.V.C. Prasad、Ming Zheng、Shikha Vig、Carl Bergstrom、David W. Smith、Qi Gao、Suresh Yeola、Craig T. Polson、Jason A. Corsa、Valerie L. Guss、Alice Loo、Jian Wang、Bogdan G. Sleczka、Charles Dangler、Barbara J. Robertson、Joseph P. Hendrick、Susan B. Roberts、Donna M. Barten

  DOI：10.1016/j.bmcl.2007.04.082

  日期：2007.7

  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.