(S)-2-(2-(3,5-difluorophenyl)acetamido)-N-((3S,7R,Z)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl)propanamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-(2-(3,5-difluorophenyl)acetamido)-N-((3S,7R,Z)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl)propanamide
• 英文别名: N2-[(3,5-difluorophenyl)acetyl]-N1-[(3S,7R)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-L-alaninamide；N~2~-[(3,5-Difluorophenyl)acetyl]-N-[(3s,7r)-1-Methyl-2-Oxo-7-Phenyl-2,3,4,7-Tetrahydro-1h-Azepin-3-Yl]-L-Alaninamide；(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(2R,6S)-1-methyl-7-oxo-2-phenyl-5,6-dihydro-2H-azepin-6-yl]propanamide
• 化学式: C₂₄H₂₅F₂N₃O₃
• 分子量: 441.478
• InChiKey: XGCLGFYBNGRVHO-ONGXBYRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  78.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-benzylidenemethylamine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 、 甲苯 为溶剂， 反应 56.0h， 生成 (S)-2-(2-(3,5-difluorophenyl)acetamido)-N-((3S,7R,Z)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl)propanamide
  参考文献：
  名称：

  Novel broad-spectrum inhibitors of bacterial methionine aminopeptidase

  摘要：

  With increasing emergence of multi-drug resistant infections, there is a dire need for new classes of compounds that act through unique mechanisms. In this work, we describe the discovery and optimization of a novel series of inhibitors of bacterial methionine aminopeptidase (MAP). Through a high-throughput screening campaign, one azepinone amide hit was found that resembled the native peptide substrate and possessed moderate biochemical potency against three bacterial isozymes. X-ray crystallography was used in combination with substrate-based design to direct the rational optimization of analogs with sub-micromolar potency. The novel compounds presented here represent potent broad-spectrum biochemical inhibitors of bacterial MAP and have the potential to lead to the development of new medicines to combat serious multi-drug resistant infections. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.05.061

文献信息

• [EN] NOVEL LACTAMS AND USES THEREOF<br/>[FR] NOUVEAUX LACTAMES ET LEURS UTILISATIONS
  申请人：ASTRAZENECA AB

  公开号：WO2004080983A1

  公开（公告）日：2004-09-23

  This invention relates to novel compounds having formula (I) to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit secretase and thereby inhibit the production of amyloid ß protein, thereby acting to prevent the formation of neurological deposits of amyloid protein. The present invention relates to the treatment of neurological disorders related to amyloid ß - protein production such as Alzheimer's disease.

  本发明涉及具有式（I）的新化合物，其药物组合物以及它们的使用方法。这些新化合物抑制分泌酶，从而抑制淀粉样β蛋白的产生，从而防止神经沉积物的形成。本发明涉及与淀粉样β蛋白产生相关的神经系统疾病的治疗，如阿尔茨海默病。
• Novel lactams and uses thereof
  申请人：Herzog John Keith

  公开号：US20060183732A1

  公开（公告）日：2006-08-17

  This invention relates to novel compounds having formula (I) to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit secretase and thereby inhibit the production of amyloid β protein, thereby acting to prevent the formation of neurological deposits of amyloid protein. The present invention relates to the treatment of neurological disorders related to amyloid β-protein production such as Alzheimer's disease.

  本发明涉及具有式（I）的新型化合物，以及它们的制药组合物和使用方法。这些新型化合物抑制分泌酶，从而抑制淀粉样β蛋白的产生，从而防止神经沉积物的淀粉样蛋白的形成。本发明涉及与淀粉样β蛋白产生相关的神经系统疾病的治疗，如阿尔茨海默病。
• US7342007B2
  申请人：——

  公开号：US7342007B2

  公开（公告）日：2008-03-11
• Novel broad-spectrum inhibitors of bacterial methionine aminopeptidase
  作者：Jonathan A. Rose、Sushmita D. Lahiri、David C. McKinney、Rob Albert、Marshall L. Morningstar、Adam B. Shapiro、Stewart L. Fisher、Paul R. Fleming

  DOI：10.1016/j.bmcl.2015.05.061

  日期：2015.8

  With increasing emergence of multi-drug resistant infections, there is a dire need for new classes of compounds that act through unique mechanisms. In this work, we describe the discovery and optimization of a novel series of inhibitors of bacterial methionine aminopeptidase (MAP). Through a high-throughput screening campaign, one azepinone amide hit was found that resembled the native peptide substrate and possessed moderate biochemical potency against three bacterial isozymes. X-ray crystallography was used in combination with substrate-based design to direct the rational optimization of analogs with sub-micromolar potency. The novel compounds presented here represent potent broad-spectrum biochemical inhibitors of bacterial MAP and have the potential to lead to the development of new medicines to combat serious multi-drug resistant infections. (C) 2015 Elsevier Ltd. All rights reserved.