N-(5-tert-butyl-2-methylphenyl)-7-methyl-2-{4-[(6-methylpyrimidin-4-yl)oxy]piperidin-1-yl}-7H-purin-6-amine | 1208252-32-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N-(5-tert-butyl-2-methylphenyl)-7-methyl-2-{4-[(6-methylpyrimidin-4-yl)oxy]piperidin-1-yl}-7H-purin-6-amine
• 英文别名: N-(5-tert-butyl-2-methylphenyl)-7-methyl-2-[4-(6-methylpyrimidin-4-yl)oxypiperidin-1-yl]purin-6-amine
• CAS: 1208252-32-7
• 化学式: C₂₇H₃₄N₈O
• 分子量: 486.62
• InChiKey: KILBBASWIGWNGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  93.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-甲基-6-(哌啶-4-氧基)嘧啶 、 N-(5-tert-butyl-2-methylphenyl)-2-chloro-7-methyl-7H-purin-6-amine 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 2.0h， 以45%的产率得到N-(5-tert-butyl-2-methylphenyl)-7-methyl-2-{4-[(6-methylpyrimidin-4-yl)oxy]piperidin-1-yl}-7H-purin-6-amine
  参考文献：
  名称：

  [EN] PURINE DERIVATIVES FOR TREATMENT OF ALZHEIMER'S DISEASE
  [FR] DÉRIVÉS DE PURINE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER

  摘要：

  这项发明涵盖了嘌呤衍生物作为γ-分泌酶调节剂，用于治疗与大脑中β-淀粉样肽沉积相关的疾病，如阿尔茨海默病，或预防或延迟与这些疾病相关的痴呆的发作。药物组合物和使用方法也包括在内。

  公开号：

  WO2010019392A1

文献信息

• [EN] PURINE DERIVATIVES FOR TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] DÉRIVÉS DE PURINE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK SHARP & DOHME

  公开号：WO2010019392A1

  公开（公告）日：2010-02-18

  The invention encompasses purine derivatives as gamma secretase modulators, useful for treating diseases associated with the deposition of beta-amyloid peptide in the brain, such as Alzheimer's disease, or of preventing or delaying the onset of dementia associated with such diseases. Pharmaceutical compositions and methods of use are included.

  这项发明涵盖了嘌呤衍生物作为γ-分泌酶调节剂，用于治疗与大脑中β-淀粉样肽沉积相关的疾病，如阿尔茨海默病，或预防或延迟与这些疾病相关的痴呆的发作。药物组合物和使用方法也包括在内。
• PURINE DERIVATIVES FOR TREATMENT OF ALZHEIMER'S DISEASE
  申请人：Rivkin Alexey A.

  公开号：US20110251172A1

  公开（公告）日：2011-10-13

  The invention encompasses purine derivatives as gamma secretase modulators, useful for treating diseases associated with the deposition of beta-amyloid peptide in the brain, such as Alzheimer's disease, or of preventing or delaying the onset of dementia associated with such diseases. Pharmaceutical compositions and methods of use are included.

  该发明涵盖了作为γ-分泌酶调节剂的嘌呤衍生物，用于治疗与在大脑中沉积β-淀粉样肽相关的疾病，例如阿尔茨海默病，或预防或延缓与此类疾病相关的痴呆的发生。其中包括药物组成和使用方法。
• Purine derivatives as potent γ-secretase modulators
  作者：Alexey Rivkin、Sean P. Ahearn、Stephanie M. Chichetti、Christopher L. Hamblett、Yudith Garcia、Michelle Martinez、Jed L. Hubbs、Michael H. Reutershan、Matthew H. Daniels、Phieng Siliphaivanh、Karin M. Otte、Chaomin Li、Andrew Rosenau、Laura M. Surdi、Joon Jung、Bethany L. Hughes、Jamie L. Crispino、George N. Nikov、Richard E. Middleton、Christopher M. Moxham、Alexander A. Szewczak、Sanjiv Shah、Lily Y. Moy、Candia M. Kenific、Flobert Tanga、Jonathan C. Cruz、Paula Andrade、Minilik H. Angagaw、Nirah H. Shomer、Thomas Miller、Benito Munoz、Mark S. Shearman

  DOI：10.1016/j.bmcl.2010.02.008

  日期：2010.4

  The development of a novel series of purines as gamma-secretase modulators for potential use in the treatment of Alzheimer's disease is disclosed herein. Optimization of a previously disclosed pyrimidine series afforded a series of potent purine-based gamma-secretase modulators with 300- to 2000-fold in vitro selectivity over inhibition of Notch cleavage and that selectively reduces A beta 42 in an APP-YAC transgenic mouse model. (C) 2010 Elsevier Ltd. All rights reserved.