1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine | 1229024-57-0

• 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-1H-imidazo[4,5-c]quinolin-4-amine
• 英文别名: Bbiq；1-benzyl-2-butylimidazo[4,5-c]quinolin-4-amine
• CAS: 1229024-57-0
• 化学式: C₂₁H₂₂N₄
• 分子量: 330.432
• InChiKey: CQBDMXYZNLJUFT-UHFFFAOYSA-N

物化性质

• 沸点：
  584.4±40.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 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：
  56.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,4-二氯-3-硝基喹啉 在 palladium on activated charcoal 、 氢气 、 sodium sulfate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 10.5h， 生成 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine
  参考文献：
  名称：

  Efficacy of TLR7 agonistic imidazoquinoline as immunochemotherapeutic agent against P. Berghei ANKA infected rodent host

  摘要：

  Malaria is a serious disease and is one of the most alarming public health issues. Plasmodium is being resistant to various antimalarials including Chloroquine (CQ) which was the first-line therapy for malaria treatment. WHO recommended several combination therapies but declining efficacy was reported to many of these therapies. Despite a great amount of research, efficient malaria vaccine still seems to be a distant dream. Immunochemotherapy could be an alternate strategy to deal with malaria. Based on the differential activity of various cytokines in the pathogenesis of and protection against malaria, the efficacy of highly active TLR7 agonistic imidazoquinoline (BBIQ) in combination with a suboptimal dose of CQ against P. berghei ANKA (PbA) in vivo was investigated. In mice treated with CQ alone, parasite appeared on Day 17 and all mice of this group died by Day 21. Whereas, mice treated with BBIQ along with CQ exhibited no appearance of parasite till Day 23. Frequencies of T cells (CD3(+), CD4(+) and CD8(+)) and T regulatory cells (CD4(+), CD25 (+) and FoxP3(+)) were found to be lower in brain of BBIQ + CQ treated mice as compared to BBIQ alone and CQ alone treated mice on Day 10. Inhibition of infiltration of inflammatory T cells and activation of T helper and T cytotoxic cells against the parasite was observed in the mice treated with this combination therapy. Serum levels of IFN-gamma and IL-12 were found to be higher on same day in mice treated with BBIQ + CQ which revealed the generation of strong Th1 immune response in mice against the infection. Overall, TLR7 agonist acted as an efficient partner when combined with potent antimalarial drug.

  DOI：

  10.1016/j.bmcl.2019.02.029

文献信息

• CLEAVABLE CONJUGATES OF TLR7/8 AGONIST COMPOUNDS, METHODS FOR PREPARATION, AND USES THEREOF
  申请人：Dynavax Technologies Corporation

  公开号：US20190151462A1

  公开（公告）日：2019-05-23

  The present disclosure relates to cleavable conjugates (for example, particle-based or antibody-based conjugates) of TLR7/8 agonists (for example, 1H-imidazo[4,5-c]quinoline derivatives) containing a conjugation linker, a cleavable linker, and a self-eliminating linker. The present disclosure also related to methods for preparation of the cleavable conjugates, uses thereof for stimulating an effective immune response, and uses thereof for the treatment of cancer.

  本公开涉及可切割的结合物（例如，基于颗粒或抗体的结合物），其中包含TLR7/8激动剂（例如，1H-咪唑[4,5-c]喹啉衍生物），包括结合连接物、可切割连接物和自消除连接物。本公开还涉及制备可切割结合物的方法，以及将其用于刺激有效的免疫反应和用于癌症治疗的用途。
• [EN] TOLL-LIKE RECEPTOR AGONISTS<br/>[FR] AGONISTES DE RÉCEPTEURS DE TYPE TOLL
  申请人：UNIV KANSAS

  公开号：WO2015023958A1

  公开（公告）日：2015-02-19

  Compounds described herein can be used for therapeutic purposes. The compounds can be TLR agonists, such as TLR7 or TLR8 agonists. The compounds can be included in pharmaceutical compositions and used for therapies were being a TLR agonist is useful. The pharmaceutical compositions can include any ingredients, such as carries, diluents, excipients, fillers or the like that are common in pharmaceutical compositions. The compounds can be those illustrated or described herein as well as derivatives thereof, prodrugs thereof, salts thereof, or stereoisomers thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combinations thereof. As such, the compounds can be used as adjuvants in vaccines, as well as for other therapeutic purposes described herein.

  本文描述的化合物可用于治疗目的。这些化合物可以是TLR激动剂，例如TLR7或TLR8激动剂。这些化合物可以包含在药物组合物中，并用于需要作为TLR激动剂有用的治疗中。药物组合物可以包括任何成分，如载体、稀释剂、赋形剂、填料或类似的在药物组合物中常见的成分。这些化合物可以是本文所示或描述的化合物，以及其衍生物、前药、盐、立体异构体，或在任何手性中心具有任何手性，或互变异构体、多晶形、溶剂化合物，或其组合。因此，这些化合物可以用作疫苗的佐剂，以及用于本文描述的其他治疗目的。
• [EN] TOLL-LIKE RECEPTOR 8 AGONISTS<br/>[FR] AGONISTES DES RÉCEPTEURS TOLL-LIKE 8
  申请人：UNIV KANSAS

  公开号：WO2015095780A1

  公开（公告）日：2015-06-25

  Compounds described herein can be used for therapeutic purposes. The compounds can be TLR agonists, such as TLR8 agonists. The compounds can be included in pharmaceutical compositions and used for therapies were being a TLR8 agonist is useful. The pharmaceutical compositions can include any ingredients, such as carries, diluents, excipients, fillers or the like that are common in pharmaceutical compositions. The compounds can be those illustrated or described herein as well as derivative thereof, prodrug thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combinations thereof. As such, the compounds can be used as adjuvants in vaccines as well as for other therapeutic purposes described herein. The compounds can have any one of the formulae described herein or derivative thereof.

  本文描述的化合物可用于治疗目的。这些化合物可以是TLR激动剂，例如TLR8激动剂。这些化合物可以包含在药物组合物中，并用于治疗需要TLR8激动剂的情况。药物组合物可以包括任何成分，例如载体、稀释剂、赋形剂、填料或其他在药物组合物中常见的成分。这些化合物可以是本文所述的化合物，以及其衍生物、前药、盐、立体异构体，或在任何手性中心具有任何手性，或互变异构体、多晶形态、溶剂合剂，或其组合。因此，这些化合物可以用作疫苗的辅助剂，以及用于本文描述的其他治疗目的。这些化合物可以具有本文描述的任何一个化学式或其衍生物。
• TOLL-LIKE RECEPTOR AGONISTS
  申请人：DAVID Sunil Abraham

  公开号：US20160166681A1

  公开（公告）日：2016-06-16

  Compounds described herein can be used for therapeutic purposes. The compounds can be TLR agonists, such as TLR7 or TLR8 agonists. The compounds can be included in pharmaceutical compositions and used for therapies were being a TLR agonist is useful. The pharmaceutical compositions can include any ingredients, such as carries, diluents, excipients, fillers or the like that are common in pharmaceutical compositions. The compounds can be those illustrated or described herein as well as derivative thereof, prodrug thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combinations thereof. As such, the compounds can be used as adjuvants in vaccines as well as for other therapeutic purposes described herein. The compounds can have any one of the formulae. Examples of the compounds can be reviewed in Table 1 and Table A1 for activates.

  本文所描述的化合物可用于治疗目的。这些化合物可以是TLR激动剂，例如TLR7或TLR8激动剂。这些化合物可以包含在制药组合物中，并用于需要TLR激动剂的治疗中。制药组合物可以包括任何常见于制药组合物中的成分，例如载体、稀释剂、辅料、填充剂或类似物。这些化合物可以是本文所示或描述的化合物，以及其衍生物、前药、盐、立体异构体或在任何手性中心具有任何手性，互变异构体、多晶形、溶剂化物或其组合。因此，这些化合物可以用作疫苗佐剂以及本文中描述的其他治疗目的。这些化合物可以具有以下任何一个式子。化合物的例子可以在表1和表A1中查看。
• Toll-like receptor agonists
  申请人：The University of Kansas

  公开号：US10471139B2

  公开（公告）日：2019-11-12

  Compounds described herein can be used for therapeutic purposes. The compounds can be TLR agonists, such as TLR7 or TLR8 agonists. The compounds can be included in pharmaceutical compositions and used for therapies were being a TLR agonist is useful. The pharmaceutical compositions can include any ingredients, such as carries, diluents, excipients, fillers or the like that are common in pharmaceutical compositions. The compounds can be those illustrated or described herein as well as derivative thereof, prodrug thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combinations thereof. As such, the compounds can be used as adjuvants in vaccines as well as for other therapeutic purposes described herein. The compounds can have any one of the formulae. Examples of the compounds can be reviewed in Table 1 and Table A1 for activates.

  本文所述化合物可用于治疗目的。这些化合物可以是 TLR 激动剂，如 TLR7 或 TLR8 激动剂。这些化合物可包含在药物组合物中，用于治疗TLR激动剂有用的疾病。药物组合物可以包括任何成分，例如药物组合物中常见的载体、稀释剂、赋形剂、填料等。化合物可以是本文图示或描述的化合物，也可以是其衍生物、原药、盐或立体异构体，或在任何手性中心具有任何手性的化合物，或同系物、多晶型物、溶胶或其组合。因此，这些化合物可用作疫苗佐剂，也可用于本文所述的其他治疗目的。这些化合物可以具有任意一个式子。化合物的实例可参见表 1 和表 A1 中的活化剂。