tert-butyl ethyl((1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl)methyl)carbamate | 1159840-73-9

• 英文名称: tert-butyl ethyl((1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl)methyl)carbamate
• CAS: 1159840-73-9
• 化学式: C₂₂H₃₀N₄O₃
• 分子量: 398.505
• InChiKey: BPVIVLRKJKZJHQ-UHFFFAOYSA-N

物化性质

• 沸点：
  579.6±40.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

反应信息

• 作为反应物：
  描述：

  tert-butyl ethyl((1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl)methyl)carbamate 在 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 0.5h， 以82%的产率得到2-((tert-butoxycarbonyl(ethyl)amino)methyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinoline 5-oxide
  参考文献：
  名称：

  Regioisomerism-dependent TLR7 agonism and antagonism in an imidazoquinoline

  摘要：

  Chronic immune activation is a hallmark of progressive HIV infection. Recent reports point to the engagement of toll-like receptor 7 (TLR7) and -9 by viral RNA as contributing to the activation of innate immune responses, which drive viral replication leading to immune exhaustion. The only known class of TLR7 antagonists is single-stranded phosphorothioate oligonucleotides, which has been demonstrated to inhibit immune activation in human and Rhesus macaque in vitro models. The availability of a selective and potent small-molecule TLR7 antagonist should allow the evaluation of potential benefits of suppression of TLR7-mediated immune activation in HIV/AIDS. Gardiquimod is a known N-1-substituted 1H-imidazoquinoline TLR7 agonist, the synthesis of which has not been published. We show that the 3H regioisomer is completely inactive as a TLR7 agonist and is weakly antagonistic. A des-amino precursor of the 3H regioisomer is more potent as a TLR7 antagonist, with an IC50 value of 7.5 mu M. This class of compound may serve as a starting point for the development of small-molecule inhibitors of TLR7. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.100
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以82 mg的产率得到tert-butyl ethyl((1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl)methyl)carbamate
  参考文献：
  名称：

  Regioisomerism-dependent TLR7 agonism and antagonism in an imidazoquinoline

  摘要：

  Chronic immune activation is a hallmark of progressive HIV infection. Recent reports point to the engagement of toll-like receptor 7 (TLR7) and -9 by viral RNA as contributing to the activation of innate immune responses, which drive viral replication leading to immune exhaustion. The only known class of TLR7 antagonists is single-stranded phosphorothioate oligonucleotides, which has been demonstrated to inhibit immune activation in human and Rhesus macaque in vitro models. The availability of a selective and potent small-molecule TLR7 antagonist should allow the evaluation of potential benefits of suppression of TLR7-mediated immune activation in HIV/AIDS. Gardiquimod is a known N-1-substituted 1H-imidazoquinoline TLR7 agonist, the synthesis of which has not been published. We show that the 3H regioisomer is completely inactive as a TLR7 agonist and is weakly antagonistic. A des-amino precursor of the 3H regioisomer is more potent as a TLR7 antagonist, with an IC50 value of 7.5 mu M. This class of compound may serve as a starting point for the development of small-molecule inhibitors of TLR7. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.100