1-((4-amino-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl)methyl)-3-(3-(dimethylamino)propyl)-1,2-diethylguanidine | 1229024-40-1

• 英文名称: 1-((4-amino-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl)methyl)-3-(3-(dimethylamino)propyl)-1,2-diethylguanidine
• 英文别名: 1-[[4-Amino-1-(2-hydroxy-2-methylpropyl)imidazo[4,5-c]quinolin-2-yl]methyl]-2-[3-(dimethylamino)propyl]-1,3-diethylguanidine
• CAS: 1229024-40-1
• 化学式: C₂₅H₄₀N₈O
• 分子量: 468.646
• InChiKey: GGLXLVAUMFNCFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(4-amino-2-((ethylamino)methyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol bis(2,2,2-trifluoroacetate) 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以24%的产率得到1-((4-amino-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl)methyl)-3-(3-(dimethylamino)propyl)-1,2-diethylguanidine
  参考文献：
  名称：

  Structure−Activity Relationships in Human Toll-Like Receptor 7-Active Imidazoquinoline Analogues

  摘要：

  Engagement of toll-like receptors serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. A structure activity study was conducted on the TLR7-agonistic imidazoquinolines, starting with 1-(4-amino-2-((ethylamino)methyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol as a lead. Modifications of the secondary amine of the C2 ethylaminomethylene side chain are poorly tolerated. The 4-amino group must be retained for activity. Replacement of the imidazole ring of the scaffold with triazole or cyclic urea led to complete loss of activity. A systematic exploration of N-1-benzyl-C2-alkyl substituents showed a very distinct relationship between alkyl length and TLR7-agonistic potency with the optimal compound bearing a C2-n-butyl group. Transposition of the N-1 and C2 substituents led to the identification of an extremely active TLR7-agonistic compound with an EC50 value of 8.6 nM. The relative potencies in human TLR7-based primary reporter gene assays were paralleled by interferon-alpha induction activities in whole human blood models.

  DOI：

  10.1021/jm100358c