tert-butyl (4-amino-3-(2-hydroxy-2-methylpropyl)-3H-imidazo[4,5-c]quinolin-2-yl)methy(ethyl)carbamate | 1159840-72-8

• 英文名称: tert-butyl (4-amino-3-(2-hydroxy-2-methylpropyl)-3H-imidazo[4,5-c]quinolin-2-yl)methy(ethyl)carbamate
• CAS: 1159840-72-8
• 化学式: C₂₂H₃₁N₅O₃
• 分子量: 413.52
• InChiKey: TXYWVLDEJKCSFE-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-amino-3-(2-hydroxy-2-methylpropyl)-3H-imidazo[4,5-c]quinolin-2-yl)methy(ethyl)carbamate 、 三氟乙酸 反应 0.58h， 以100%的产率得到1-(4-amino-2-((ethylamino)methyl)-3H-imidazo[4,5-c]quinolin-3-yl)-2-methylpropan-2-ol bis(trifluoroacetate) salt
  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：

  C₂₉H₃₅N₅O₅ 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以30 mg的产率得到tert-butyl (4-amino-3-(2-hydroxy-2-methylpropyl)-3H-imidazo[4,5-c]quinolin-2-yl)methy(ethyl)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