1-Benzyl-2-butyl-4-chloroimidazo[4,5-c]quinoline | 1229024-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-Benzyl-2-butyl-4-chloroimidazo[4,5-c]quinoline
• CAS: 1229024-68-3
• 化学式: C₂₁H₂₀ClN₃
• 分子量: 349.863
• InChiKey: VHYOJGAUPVOYRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-Benzyl-2-butyl-4-chloroimidazo[4,5-c]quinoline 在 盐酸羟胺 、 三乙胺 作用下， 以 甲醇 为溶剂， 以10 mg的产率得到N-(1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-yl)hydroxylamine
  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
• 作为产物：
  描述：

  在 calcium oxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以75 mg的产率得到1-Benzyl-2-butyl-4-chloroimidazo[4,5-c]quinoline
  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

文献信息

• TOLL-LIKE RECEPTOR-7 AND -8 MODULATORY 1H IMIDAZOQUINOLINE DERIVED COMPOUNDS
  申请人：David Sunil A.

  公开号：US20120294885A1

  公开（公告）日：2012-11-22

  The present disclosure provides novel imidazoquinoline derived compounds, derivatives thereof, analogues thereof, and pharmaceutically acceptable salts thereof, and methods of making and using such compounds. The present disclosure also provides TLR7 agonists and TLR7/TLR8 dual agonists, probes, tissue-specific molecules, adjuvants, immunogenic compositions, therapeutic compositions, and self-adjuvanting vaccines including the imidazoquinoline derived compounds, derivatives thereof, analogues thereof, and pharmaceutically acceptable salts thereof. Derivatives of the imidazoquinoline derived compounds also include dendrimers and dimers of the imidazoquinoline derived compounds, and methods of making and using the dendrimeic and dimeric imidazoquinoline derived compounds. The present disclosure also provides dual TLR2/TLR7 hybrid agonists that include imidazoquinoline derived compounds of the present disclosure.

  本公开提供了新型咪唑喹啉衍生化合物，其衍生物，类似物，以及其药用盐，并提供了制备和使用这些化合物的方法。本公开还提供了TLR7激动剂和TLR7/TLR8双激动剂，探针，组织特异性分子，佐剂，免疫原性组合物，治疗组合物，以及包括咪唑喹啉衍生化合物，其衍生物，类似物和药用盐的自佐剂疫苗。咪唑喹啉衍生化合物的衍生物还包括咪唑喹啉衍生化合物的树枝状分子和二聚体，以及制备和使用这些树枝状和二聚体咪唑喹啉衍生化合物的方法。本公开还提供了包括本公开的咪唑喹啉衍生化合物的双TLR2/TLR7混合激动剂。
• Toll-like receptor-7 and -8 modulatory 1H imidazoquinoline derived compounds
  申请人：The University of Kansas

  公开号：US10208037B2

  公开（公告）日：2019-02-19

  The present disclosure provides novel imidazoquinoline derived compounds, derivatives thereof, analogues thereof, and pharmaceutically acceptable salts thereof, and methods of making and using such compounds. The present disclosure also provides TLR7 agonists and TLR7/TLR8 dual agonists, probes, tissue-specific molecules, adjuvants, immunogenic compositions, therapeutic compositions, and self-adjuvanting vaccines including the imidazoquinoline derived compounds, derivatives thereof, analogues thereof, and pharmaceutically acceptable salts thereof. Derivatives of the imidazoquinoline derived compounds also include dendrimers and dimers of the imidazoquinoline derived compounds, and methods of making and using the dendrimeric and dimeric imidazoquinoline derived compounds. The present disclosure also provides dual TLR2/TLR7 hybrid agonists that include imidazoquinoline derived compounds of the present disclosure.

  本公开提供了新型咪唑喹啉衍生化合物、其衍生物、其类似物、其药学上可接受的盐，以及制造和使用此类化合物的方法。本公开还提供了 TLR7 激动剂和 TLR7/TLR8 双激动剂、探针、组织特异性分子、佐剂、免疫原性组合物、治疗组合物和自佐剂疫苗，包括咪唑喹啉衍生化合物、其衍生物、其类似物和其药学上可接受的盐。咪唑喹啉衍生化合物的衍生物还包括咪唑喹啉衍生化合物的树枝状分子和二聚体，以及树枝状和二聚体咪唑喹啉衍生化合物的制造和使用方法。本公开还提供了双重TLR2/TLR7混合激动剂，其中包括本公开的咪唑喹啉衍生化合物。
• Toll-Like Receptor (TLR)-7 and -8 Modulatory Activities of Dimeric Imidazoquinolines
  作者：Nikunj M. Shukla、Cole A. Mutz、Subbalakshmi S. Malladi、Hemamali J. Warshakoon、Rajalakshmi Balakrishna、Sunil A. David

  DOI：10.1021/jm2010207

  日期：2012.2.9

  Toll-like receptors (TLRs) are pattern recognition receptors that recognize specific molecular patterns present in molecules that are broadly shared by pathogens but are structurally distinct from host molecules. The TLR7-agonistic imidazoquinolines are of interest as vaccine adjuvants given their ability to induce pronounced Th1-skewed humoral responses. Minor modifications on the imidazoquinoline scaffold result in TLR7-antagonistic compounds which may be of value in addressing innate immune activation-driven immune exhaustion observed in HIV. We describe the syntheses and evaluation of TLR7 and TLR8 modulatory activities of dimeric constructs of imidazoquinoline linked at the C2, C4, C8, and N-1-aryl positions. Dinners linked at the C4, C8, and N-1-aryl positions were agonistic at TLR7; only the N-1-aryl dimer with a 12-carbon linker was dual TLR7/8 agonistic. Dimers linked at C2 position showed antagonistic activities at TLR7 and TLR8; the C2 dimer with a propylene spacer was maximally antagonistic at both TLR7 and TLR8.
• US20140256922A1
  申请人：——

  公开号：US20140256922A1

  公开（公告）日：2014-09-11
• US8728486B2
  申请人：——

  公开号：US8728486B2

  公开（公告）日：2014-05-20