N-(1-benzyl-2-butyl-1H-imidazo[4,5-c]pyridin-4-yl)acetamide | 1457966-75-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(1-benzyl-2-butyl-1H-imidazo[4,5-c]pyridin-4-yl)acetamide
• 英文别名: N-(1-benzyl-2-butylimidazo[4,5-c]pyridin-4-yl)acetamide
• CAS: 1457966-75-4
• 化学式: C₁₉H₂₂N₄O
• 分子量: 322.41
• InChiKey: PHNLFULXBGWSJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氨基-4-(苄氨基)吡啶 在 三乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 、 苯甲酰异氰酸脂 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 13.0h， 生成 N-(1-benzyl-2-butyl-1H-imidazo[4,5-c]pyridin-4-yl)acetamide
  参考文献：
  名称：

  Structure–activity relationships in Toll-like receptor 7 agonistic 1H-imidazo[4,5-c]pyridines

  摘要：

  TLR7在浆细胞样树突细胞中的激活导致IFN-α/β的诱导，这在调控适应性免疫中发挥了关键作用。我们之前已研究了TLR7/8激动剂咪唑喹啉的结构-活性关系（SAR），重点关注N1、C2、N3和N4位置的取代基，现在我们报告1H-咪唑[4,5-c]吡啶的SAR。发现1-苄基-2-丁基-1H-咪唑[4,5-c]吡啶-4-胺为纯TLR7激动剂，且对TLR8的活性微乎其微。在N6取代的类似物中观察到活性增加，特别是在那些具有富电子取代基的化合物中。C6的直接芳基-芳基连接抑制了活性，但在6-苄基和6-苯乙基类似物中恢复了TLR7激动活性。与纯TLR7激动剂行为一致，在人PBMC中观察到显著的IFN-α诱导，同时引起的促炎细胞因子诱导很少。还合成了一种咪唑喹啉的苯类化合物，其在效能上显著优于母体咪唑吡啶。在N6取代的类似物中，关于人PBMC的IFN-α诱导和淋巴细胞亚群中CD69上调的差异明显。

  DOI：

  10.1039/c3ob40816g

文献信息

• [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。
• 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。
• Structure–activity relationships in Toll-like receptor 7 agonistic 1H-imidazo[4,5-c]pyridines
  作者：Euna Yoo、Breanna M. Crall、Rajalakshmi Balakrishna、Subbalakshmi S. Malladi、Lauren M. Fox、Alec R. Hermanson、Sunil A. David

  DOI：10.1039/c3ob40816g

  日期：——

  Engagement of TLR7 in plasmacytoid dendritic cells leads to the induction of IFN-α/β which plays essential functions in the control of adaptive immunity. We had previously examined structure–activity relationships (SAR) in TLR7/8-agonistic imidazoquinolines with a focus on substituents at the N1, C2, N3 and N4 positions, and we now report SAR on 1H-imidazo[4,5-c]pyridines. 1-Benzyl-2-butyl-1H-imidazo[4,5-c]pyridin-4-amine was found to be a pure TLR7-agonist with negligible activity on TLR8. Increase in potency was observed in N6-substituted analogues, especially in those compounds with electron-rich substituents. Direct aryl–aryl connections at C6 abrogated activity, but TLR7 agonism was reinstated in 6-benzyl and 6-phenethyl analogues. Consistent with the pure TLR7-agonistic behavior, prominent IFN-α induction in human PBMCs was observed with minimal proinflammatory cytokine induction. A benzologue of imidazoquinoline was also synthesized which showed substantial improvements in potency over the parent imidazopyridine. Distinct differences in N6-substituted analogues were observed with respect to IFN-α induction in human PBMCs on the one hand, and CD69 upregulation in lymphocytic subsets, on the other.

  TLR7在浆细胞样树突细胞中的激活导致IFN-α/β的诱导，这在调控适应性免疫中发挥了关键作用。我们之前已研究了TLR7/8激动剂咪唑喹啉的结构-活性关系（SAR），重点关注N1、C2、N3和N4位置的取代基，现在我们报告1H-咪唑[4,5-c]吡啶的SAR。发现1-苄基-2-丁基-1H-咪唑[4,5-c]吡啶-4-胺为纯TLR7激动剂，且对TLR8的活性微乎其微。在N6取代的类似物中观察到活性增加，特别是在那些具有富电子取代基的化合物中。C6的直接芳基-芳基连接抑制了活性，但在6-苄基和6-苯乙基类似物中恢复了TLR7激动活性。与纯TLR7激动剂行为一致，在人PBMC中观察到显著的IFN-α诱导，同时引起的促炎细胞因子诱导很少。还合成了一种咪唑喹啉的苯类化合物，其在效能上显著优于母体咪唑吡啶。在N6取代的类似物中，关于人PBMC的IFN-α诱导和淋巴细胞亚群中CD69上调的差异明显。