3-(pentyloxy)quinolin-2-amine | 1607440-14-1

• 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: 3-(pentyloxy)quinolin-2-amine
• 英文别名: 3-Pentoxyquinolin-2-amine；3-pentoxyquinolin-2-amine
• CAS: 1607440-14-1
• 化学式: C₁₄H₁₈N₂O
• 分子量: 230.31
• InChiKey: CRKSKSMMNIFHSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  48.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-羟基喹啉 在 potassium carbonate 、 间氯过氧苯甲酸 、 苯甲酰异氰酸脂 作用下， 以 二氯甲烷 、 氯仿 、 二甲基亚砜 为溶剂， 反应 11.0h， 生成 3-(pentyloxy)quinolin-2-amine
  参考文献：
  名称：

  Structure-Based Design of Novel Human Toll-like Receptor 8 Agonists

  摘要：

  AbstractToll‐like receptor (TLR)‐8 agonists activate adaptive immune responses by inducing robust production of T helper 1‐polarizing cytokines, suggesting that TLR8‐active compounds might be promising candidate vaccine adjuvants. Recently, a C2‐butyl furo[2,3‐c]quinoline was reported with purely TLR8 agonistic activity. This compound was successfully co‐crystallized with the human TLR8 ectodomain, and the co‐crystal structure revealed ligand‐induced reorganization of the binding pocket of TLR8. The loss of a key hydrogen bond between the oxygen atom of the furanyl ring of the agonist and Thr 574 in TLR8 suggested that the furan ring is dispensable. Employing a disconnection strategy, 3‐ and 4‐substituted aminoquinolines were investigated. Focused structure‐based ligand design studies led to the identification of 3‐pentyl‐quinoline‐2‐amine as a novel, structurally simple, and highly potent human TLR8‐specific agonist (EC50=0.2 μM). Preliminary evaluation of this compound in ex vivo human blood assay systems revealed that it retains prominent cytokine‐inducing activity. Together, these results indicate the suitability of this compound as a novel vaccine adjuvant, warranting further investigation.

  DOI：

  10.1002/cmdc.201300573

文献信息

• [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 8 agonists
  申请人：The University Of Kansas

  公开号：US10654807B2

  公开（公告）日：2020-05-19

  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 TLR8 激动剂。这些化合物可以包含在药物组合物中，用于治疗TLR8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、填料或类似物。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本文所述的任何一种式子或其衍生物。
• Toll-Like Receptor 8 Agonists
  申请人：David Sunil Abraham

  公开号：US20160347715A1

  公开（公告）日：2016-12-01

  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.
• Structure-Based Design of Novel Human Toll-like Receptor 8 Agonists
  作者：Hari Prasad Kokatla、Diptesh Sil、Hiromi Tanji、Umeharu Ohto、Subbalakshmi S. Malladi、Lauren M. Fox、Toshiyoki Shimizu、Sunil A. David

  DOI：10.1002/cmdc.201300573

  日期：2014.4

  AbstractToll‐like receptor (TLR)‐8 agonists activate adaptive immune responses by inducing robust production of T helper 1‐polarizing cytokines, suggesting that TLR8‐active compounds might be promising candidate vaccine adjuvants. Recently, a C2‐butyl furo[2,3‐c]quinoline was reported with purely TLR8 agonistic activity. This compound was successfully co‐crystallized with the human TLR8 ectodomain, and the co‐crystal structure revealed ligand‐induced reorganization of the binding pocket of TLR8. The loss of a key hydrogen bond between the oxygen atom of the furanyl ring of the agonist and Thr 574 in TLR8 suggested that the furan ring is dispensable. Employing a disconnection strategy, 3‐ and 4‐substituted aminoquinolines were investigated. Focused structure‐based ligand design studies led to the identification of 3‐pentyl‐quinoline‐2‐amine as a novel, structurally simple, and highly potent human TLR8‐specific agonist (EC50=0.2 μM). Preliminary evaluation of this compound in ex vivo human blood assay systems revealed that it retains prominent cytokine‐inducing activity. Together, these results indicate the suitability of this compound as a novel vaccine adjuvant, warranting further investigation.