[2-oxo-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]carbamic acid benzyl ester | 682812-79-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: [2-oxo-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]carbamic acid benzyl ester
• 英文别名: [2-Oxo-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-carbamic Acid Benzyl Ester；benzyl N-[2-oxo-5-[4-(trifluoromethyl)phenyl]-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate
• CAS: 682812-79-9
• 化学式: C₂₄H₁₈F₃N₃O₃
• 分子量: 453.42
• InChiKey: KYFSBKNGKDYOPE-UHFFFAOYSA-N

物化性质

• 沸点：
  613.6±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  79.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [2-oxo-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]carbamic acid benzyl ester 在 氢溴酸 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 2-methoxy-N-[2-oxo-5-[4-(trifluoromethyl)phenyl]-1,3-dihydro-1,4-benzodiazepin-3-yl]benzamide
  参考文献：
  名称：

  1,4-Benzodiazepines as Inhibitors of Respiratory Syncytial Virus

  摘要：

  Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC50's less than 50 mu M. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.

  DOI：

  10.1021/jm051185t
• 作为产物：
  描述：

  N-(2-(4-(trifluoromethyl)benzoyl)phenyl)acetamide 在 N-甲基吗啉 、 盐酸 、 ammonium hydroxide 、 草酰氯 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 [2-oxo-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]carbamic acid benzyl ester
  参考文献：
  名称：

  Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides as potent γ-secretase inhibitors

  摘要：

  We report the synthesis of benzoazepine-derived cyclic malonamides (2) and aminoamides (3) as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease. The in vitro structure-activity relationships of 2 and 3 along with dog pharmacokinetic results are described. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.102

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。
• US7001901B2
  申请人：——

  公开号：US7001901B2

  公开（公告）日：2006-02-21
• 1,4-Benzodiazepines as Inhibitors of Respiratory Syncytial Virus
  作者：Malcolm C. Carter、Dagmar G. Alber、Robert C. Baxter、Sian K. Bithell、Jo Budworth、Ann Chubb、G. Stuart Cockerill、Verity C. L. Dowdell、Elisa A. Henderson、Sally J. Keegan、Richard D. Kelsey、Michael J. Lockyer、Jeremy N. Stables、Lara J. Wilson、Kenneth L. Powell

  DOI：10.1021/jm051185t

  日期：2006.4.1

  Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC50's less than 50 mu M. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.
• Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides as potent γ-secretase inhibitors
  作者：Michael G. Yang、Jian-Liang Shi、Dilip P. Modi、Jennifer Wells、Brian M. Cochran、Mark A. Wolf、Lorin A. Thompson、Mercy M. Ramanjulu、Arthur H. Roach、Robert Zaczek、David W. Robertson、Ruth R. Wexler、Richard E. Olson

  DOI：10.1016/j.bmcl.2007.04.102

  日期：2007.7

  We report the synthesis of benzoazepine-derived cyclic malonamides (2) and aminoamides (3) as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease. The in vitro structure-activity relationships of 2 and 3 along with dog pharmacokinetic results are described. (C) 2007 Elsevier Ltd. All rights reserved.