6-ethyl-1-methyl-1,6-dihydro[1,2]thiazepino[5,4,3-cd]indole-8-carboxylic acid 2,2-dioxide | 856695-97-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-ethyl-1-methyl-1,6-dihydro[1,2]thiazepino[5,4,3-cd]indole-8-carboxylic acid 2,2-dioxide
• 英文别名: 3-ethyl-9-methyl-10,10-dioxo-10λ6-thia-3,9-diazatricyclo[6.4.1.04,13]trideca-1,4(13),5,7,11-pentaene-6-carboxylic acid
• CAS: 856695-97-1
• 化学式: C₁₄H₁₄N₂O₄S
• 分子量: 306.342
• InChiKey: CIIXDAUIPSFUGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  88
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-ethyl-1-methyl-1,6-dihydro[1,2]thiazepino[5,4,3-cd]indole-8-carboxylic acid 2,2-dioxide 在 10% palladium on activated carbon 、 ammonium acetate 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以77%的产率得到6-ethyl-1-methyl-1,3,4,6-tetrahydro[1,2]thiazepino[5,4,3-cd]indole-8-carboxylic acid 2,2-dioxide
  参考文献：
  名称：

  Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics

  摘要：

  Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improved pharmacokinetic profiles. In this Letter, we describe our successful strategy for the optimization of oral bioavailability and also give insights into the design of compounds with the potential for improved brain penetration.

  DOI：

  10.1016/j.bmcl.2009.03.149
• 作为产物：
  描述：

  6-ethyl-1-methyl-1,6-dihydro[1,2]thiazepino[5,4,3-cd]indole-3,8-dicarboxylic acid 2,2-dioxide 在 水 、 乙醚 、 乙酸乙酯 作用下， 以 盐酸 、 1,4-二氧六环 为溶剂， 反应 1.0h， 以with ether again to give the title compound (A3) as a pale yellow solid (1.75 g)的产率得到6-ethyl-1-methyl-1,6-dihydro[1,2]thiazepino[5,4,3-cd]indole-8-carboxylic acid 2,2-dioxide
  参考文献：
  名称：

  Tricycle indole hydroxyethlamine derivatives and their use in the treatment of alzheimer's disease

  摘要：

  本发明涉及一种新型的羟乙基胺化合物，具有Asp2（β-分泌酶，BACE1或Memapsin）抑制活性，其制备过程，包含它们的组合物和它们在治疗由高β-淀粉样蛋白水平或β-淀粉样蛋白沉积物所特征的疾病，尤其是阿尔茨海默病中的应用。

  公开号：

  US20070073060A1

文献信息

• [EN] TRICYCLIC INDOLE HYDROXYETHYLAMINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] DERIVES D'INDOLE HYDROXYETHYLAMINE TRICYCLIQUES ET LEUR UTILISATION DANS LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：GLAXO GROUP LTD

  公开号：WO2005058915A1

  公开（公告）日：2005-06-30

  The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity of formula (I), 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. Formula (I) wherein, inter alia, A-B represents -NR5-SO2- or -NR5-CO-; R5 represents hydrogen, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-10 cycloalkyl, -C0-6 alkylaryl, -C0-6 alkyl-heteroaryl, -C0-6 alkyl-heterocyclyl, -C3-10 cycloalkyl-aryl or -C3-10 cycloalkyl-heteroaryl; -W- represents -CH2-, -(CH2)2-, -(CH2)3-, -C(H)=C(H)- or -CH2-C(H)=C(H)-; X-Y-Z represents -C=CR8-NR9-;

  该发明涉及具有Asp2（β-分泌酶，BACE1或Memapsin）抑制活性的新型羟乙基胺化合物的公式（I），其制备方法，含有它们的组合物以及它们在治疗由β-淀粉样蛋白水平或β-淀粉样蛋白沉积增高所特征化的疾病，特别是阿尔茨海默病中的用途。公式（I）中，A-B代表-NR5-SO2-或-NR5-CO-；R5代表氢，C1-6烷基，C3-6烯基，C3-6炔基，C3-10环烷基，-C0-6烷基芳基，-C0-6烷基-杂芳基，-C0-6烷基-杂环烷基，-C3-10环烷基-芳基或-C3-10环烷基-杂芳基；-W-代表-CH2-，-( )2-，-( )3-，-C(H)=C(H)-或- -C(H)=C(H)-；X-Y-Z代表-C=CR8-NR9-；
• TRICYCLIC INDOLE HYDROXYETHYLAMINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF ALZHEIMER'S DISEASE
  申请人：GLAXO GROUP LIMITED

  公开号：EP1692143A1

  公开（公告）日：2006-08-23