methyl {3-[(6-amino-8-bromo-2-butoxy-9H-purin-9-yl)methyl]phenyl}acetate | 1218987-99-5

• 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: methyl {3-[(6-amino-8-bromo-2-butoxy-9H-purin-9-yl)methyl]phenyl}acetate
• 英文别名: Methyl 2-[3-[(6-amino-8-bromo-2-butoxypurin-9-yl)methyl]phenyl]acetate
• CAS: 1218987-99-5
• 化学式: C₁₉H₂₂BrN₅O₃
• 分子量: 448.319
• InChiKey: CNAYIUDMNPIHKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl {3-[(6-amino-8-bromo-2-butoxy-9H-purin-9-yl)methyl]phenyl}acetate 在 sodium hydroxide 、 硫酸 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以77%的产率得到2-butoxy-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 8-Oxoadenine Derivatives as Toll-like Receptor 7 Agonists Introducing the Antedrug Concept

  摘要：

  Systemic administration of a Toll-like receptor 7 (TLR7) agonist is effective to in suppressing Th2 derived inflammation, however systemic induction of various cytokines such as IL-6, IL-12, and type I interferon (IFN) is observed. This cytokine induction would be expected to cause flu-like symptoms. We have previously reported adenine compounds (3, 4) as interferon inducing agents acting as TLR7 agonists. To identify potent anti-inflammatory compounds without systemic side effects, a labile carboxylic ester as an antedrug functionality onto the N(9)-benzyl group of the adenine was introduced. We found that 9e was a potent TLR7 agonist (EC(50) 50 nM) and rapidly metabolized by human plasma (T(1/2)2.6 min) to the pharmacologically much less active carboxylic acid 16. Intratracheal administration of 9e effectively inhibited allergen-induced airway inflammation without inducing cytokines systemically. Therefore, the TLR7 agonist with antedrug characteristics 9e (SM-324405) is a novel candidate for immunotherapy of allergic diseases.

  DOI：

  10.1021/jm100070n
• 作为产物：
  描述：

  methyl {3-[(6-amino-2-butoxy-9H-purin-9-yl)methyl]phenyl}acetate 在 溴 、 sodium acetate 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以86%的产率得到methyl {3-[(6-amino-8-bromo-2-butoxy-9H-purin-9-yl)methyl]phenyl}acetate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 8-Oxoadenine Derivatives as Toll-like Receptor 7 Agonists Introducing the Antedrug Concept

  摘要：

  Systemic administration of a Toll-like receptor 7 (TLR7) agonist is effective to in suppressing Th2 derived inflammation, however systemic induction of various cytokines such as IL-6, IL-12, and type I interferon (IFN) is observed. This cytokine induction would be expected to cause flu-like symptoms. We have previously reported adenine compounds (3, 4) as interferon inducing agents acting as TLR7 agonists. To identify potent anti-inflammatory compounds without systemic side effects, a labile carboxylic ester as an antedrug functionality onto the N(9)-benzyl group of the adenine was introduced. We found that 9e was a potent TLR7 agonist (EC(50) 50 nM) and rapidly metabolized by human plasma (T(1/2)2.6 min) to the pharmacologically much less active carboxylic acid 16. Intratracheal administration of 9e effectively inhibited allergen-induced airway inflammation without inducing cytokines systemically. Therefore, the TLR7 agonist with antedrug characteristics 9e (SM-324405) is a novel candidate for immunotherapy of allergic diseases.

  DOI：

  10.1021/jm100070n

文献信息

• Synthesis and Biological Evaluation of 8-Oxoadenine Derivatives as Toll-like Receptor 7 Agonists Introducing the Antedrug Concept
  作者：Ayumu Kurimoto、Kazuki Hashimoto、Tomoaki Nakamura、Kei Norimura、Haruhisa Ogita、Haruo Takaku、Roger Bonnert、Tom McInally、Hiroki Wada、Yoshiaki Isobe

  DOI：10.1021/jm100070n

  日期：2010.4.8

  Systemic administration of a Toll-like receptor 7 (TLR7) agonist is effective to in suppressing Th2 derived inflammation, however systemic induction of various cytokines such as IL-6, IL-12, and type I interferon (IFN) is observed. This cytokine induction would be expected to cause flu-like symptoms. We have previously reported adenine compounds (3, 4) as interferon inducing agents acting as TLR7 agonists. To identify potent anti-inflammatory compounds without systemic side effects, a labile carboxylic ester as an antedrug functionality onto the N(9)-benzyl group of the adenine was introduced. We found that 9e was a potent TLR7 agonist (EC(50) 50 nM) and rapidly metabolized by human plasma (T(1/2)2.6 min) to the pharmacologically much less active carboxylic acid 16. Intratracheal administration of 9e effectively inhibited allergen-induced airway inflammation without inducing cytokines systemically. Therefore, the TLR7 agonist with antedrug characteristics 9e (SM-324405) is a novel candidate for immunotherapy of allergic diseases.