methyl 8-amino-4-ethyl-1,2,3,4-tetrahydro-6-quinoxalinecarboxylate | 706818-90-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: methyl 8-amino-4-ethyl-1,2,3,4-tetrahydro-6-quinoxalinecarboxylate
• 英文别名: Methyl 8-amino-4-ethyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylate；methyl 8-amino-4-ethyl-2,3-dihydro-1H-quinoxaline-6-carboxylate
• CAS: 706818-90-8
• 化学式: C₁₂H₁₇N₃O₂
• 分子量: 235.286
• InChiKey: VKYZRNLPUMIVCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 8-amino-4-ethyl-1,2,3,4-tetrahydro-6-quinoxalinecarboxylate 、 tBuOCOCH2SO2Cl 在 吡啶 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 以20%的产率得到
  参考文献：
  名称：

  Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent

  摘要：

  Our first generation of hydroxyethylamine transition-state mimetic BACE-1 inhibitors allowed us to validate BACE-1 as a key target for Alzheimer's disease by demonstrating amyloid lowering in an animal model, albeit at rather high doses. Finding a molecule from this series which was active at lower oral doses proved elusive and demonstrated the need to find a novel series of inhibitors with improved pharmacokinetics. This Letter describes the discovery of such inhibitors.

  DOI：

  10.1016/j.bmcl.2009.03.150
• 作为产物：
  描述：

  methyl 4-ethyl-8-nitro-1,2,3,4-tetrahydro-6-quinoxalinecarboxylate 在 10% palladium on carbon 、 甲酸铵 作用下， 以 甲醇 为溶剂， 以98%的产率得到methyl 8-amino-4-ethyl-1,2,3,4-tetrahydro-6-quinoxalinecarboxylate
  参考文献：
  名称：

  Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent

  摘要：

  Our first generation of hydroxyethylamine transition-state mimetic BACE-1 inhibitors allowed us to validate BACE-1 as a key target for Alzheimer's disease by demonstrating amyloid lowering in an animal model, albeit at rather high doses. Finding a molecule from this series which was active at lower oral doses proved elusive and demonstrated the need to find a novel series of inhibitors with improved pharmacokinetics. This Letter describes the discovery of such inhibitors.

  DOI：

  10.1016/j.bmcl.2009.03.150

文献信息

• [EN] HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] DERIVES D'HYDROXYETHYLAMINE UTILISES POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：GLAXO GROUP LTD

  公开号：WO2004050619A1

  公开（公告）日：2004-06-17

  The present invention relates to novel hydroxyethylamine compounds of formula (I): (I) having Asp2 (-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated - amyloid levels or -amyloid deposits, particularly Alzheimer's disease.

  本发明涉及具有Asp2（-分泌酶，BACE1或Memapsin）抑制活性的新型羟乙基胺化合物的化学式（I）：（I），其制备方法，含有它们的组合物以及它们在治疗由高β-淀粉样蛋白水平或β-淀粉样蛋白沉积所特征的疾病中的应用，特别是阿尔茨海默病。
• Hydroxyethylamine derivatives for the treatment of alzheimer's disease
  申请人：Demont H Emmanuel

  公开号：US20060025459A1

  公开（公告）日：2006-02-02

  The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β-amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.

  本发明涉及具有Asp2（β-秘鲁酶、BACE1或Memapsin）抑制活性的新型羟乙基胺化合物，其制备方法，包含它们的组合物以及它们在治疗由高β-淀粉样蛋白水平或β-淀粉样蛋白沉积物所特征的疾病，特别是阿尔茨海默病中的应用。
• HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE
  申请人：GLAXO GROUP LIMITED

  公开号：EP1567488B1

  公开（公告）日：2007-02-21
• US7253198B2
  申请人：——

  公开号：US7253198B2

  公开（公告）日：2007-08-07
• Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent
  作者：Nicolas Charrier、Brian Clarke、Emmanuel Demont、Colin Dingwall、Rachel Dunsdon、Julie Hawkins、Julia Hubbard、Ishrut Hussain、Graham Maile、Rosalie Matico、Julie Mosley、Alan Naylor、Alistair O’Brien、Sally Redshaw、Paul Rowland、Virginie Soleil、Kathrine J. Smith、Sharon Sweitzer、Pam Theobald、David Vesey、Daryl S. Walter、Gareth Wayne

  DOI：10.1016/j.bmcl.2009.03.150

  日期：2009.7

  Our first generation of hydroxyethylamine transition-state mimetic BACE-1 inhibitors allowed us to validate BACE-1 as a key target for Alzheimer's disease by demonstrating amyloid lowering in an animal model, albeit at rather high doses. Finding a molecule from this series which was active at lower oral doses proved elusive and demonstrated the need to find a novel series of inhibitors with improved pharmacokinetics. This Letter describes the discovery of such inhibitors.