8-bromo-N2-butyl-9-(4-nitrobenzyl)-9H-purine-2,6-diamine

• 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: 8-bromo-N2-butyl-9-(4-nitrobenzyl)-9H-purine-2,6-diamine
• 英文别名: 8-bromo-2-N-butyl-9-[(4-nitrophenyl)methyl]purine-2,6-diamine
• 化学式: C₁₆H₁₈BrN₇O₂
• 分子量: 420.269
• InChiKey: JFZLFNNJTROTHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-bromo-N2-butyl-9-(4-nitrobenzyl)-9H-purine-2,6-diamine 在 盐酸 、 palladium 10% on activated carbon 、 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 N1,N5,N10-triBoc-spermine (S)-5-(4-((6-amino-2-(butylamino)-8-hydroxy-9H-purin-9-yl)methyl)phenylamino)-4-amino-5-oxopentanamide
  参考文献：
  名称：

  Novel compositions of TLR7 and/or TLR8 agonists conjugated to lipids

  摘要：

  公开号：

  EP2674170B1
• 作为产物：
  描述：

  2-氯-6-氨基嘌呤 在 溴 、 potassium carbonate 作用下， 以 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 8-bromo-N2-butyl-9-(4-nitrobenzyl)-9H-purine-2,6-diamine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel 9-Substituted-8-Hydroxyadenine Derivatives as Potent Interferon Inducers

  摘要：

  Recently we reported the adenine derivatives 3a-d as novel interferon (IFN) inducers. In the present study, we conducted a detailed structure-activity relationship study of analogues of 3a-d with respect to their IFN-inducing activity, mainly focusing on the N(9)-position of the adenine. From this study, we found that introduction of the 3-pyridylmethyl moiety was effective to increase in vitro activity, and compound 9ae was identified as being the most potent IFN inducer. This compound gave a minimum effective concentration (MEC) of 3 nM, which is comparable with that of R-848, a second generation IFN inducer. Compound 9ae also demonstrated potent IFN-inducing activity at a dose of 0.1 mg/kg by oral administration in mice. Furthermore, compound 9ae induced IFN in monkeys in a dose dependent manner, with a potency superior to that of R-848. In addition, 9ae did not cause emesis in ferrets even at a dose of 30 mg/kg. In this study the maximum plasma concentration of 9ae was 1019 ng/mL (ca. 3.1 mu M), which was approximately 1000-fold higher than the MEC value. Therefore, with respect to both the efficacy and the safety margin, compound 9ae (SM-276001) is considered to be a promising compound as an orally active IFN inducer.

  DOI：

  10.1021/jm051089s

文献信息

• CONJUGATED TLR7 AND/OR TLR8 AND TLR2 AGONISTS
  申请人：CAYLA

  公开号：US20140141033A1

  公开（公告）日：2014-05-22

  A conjugated compound of formula Q-Z—R 4 wherein Q is a TLR7 and/or TLR8 agonist and Z—R 4 is a TLR2 agonist, and the uses thereof in the treatment of infection, cancer or immune disorders or for use in vaccines.

  一种配方为Q-Z—R4的共轭化合物，其中Q是TLR7和/或TLR8激动剂，Z—R4是TLR2激动剂，以及它们在治疗感染、癌症或免疫紊乱或用于疫苗中的用途。
• NOVEL COMPOSITIONS OF TLR7 AND/OR TLR8 AGONISTS CONJUGATED TO LIPIDS
  申请人：CAYLA

  公开号：US20130336996A1

  公开（公告）日：2013-12-19

  A conjugated compound of formula Q-Z—R 4 wherein Q is a TLR7 and/or TLR8 agonist and Z—R 4 is a lipid covalently linked to an amino acid or peptide coupled to a polyamine group, and a process for the manufacture of the conjugated compound, as well as a complex formed between the conjugated compound and a polyanionic molecule and a pharmaceutical composition containing the conjugated compound or complex. Also described is the use of the conjugated compound or complex in the treatment of infection, cancer or immune disorders or for use in vaccines.

  一种公式为Q-Z-R4的共轭化合物，其中Q是TLR7和/或TLR8激动剂，Z-R4是与氨基酸或肽偶联的脂质共价连接到多胺基团，以及制造共轭化合物的过程，以及由共轭化合物和多阴离子分子形成的复合物和含有共轭化合物或复合物的制药组合物。还描述了在治疗感染、癌症或免疫紊乱或用于疫苗中使用共轭化合物或复合物的用途。
• Conjugated TLR7 and/or TLR8 and TLR2 polycationic agonists
  申请人：Invivogen

  公开号：EP2769738B1

  公开（公告）日：2016-07-20
• US9295732B2
  申请人：——

  公开号：US9295732B2

  公开（公告）日：2016-03-29
• US9458184B2
  申请人：——

  公开号：US9458184B2

  公开（公告）日：2016-10-04