4-chloro-1-(2-chloro-6-methoxyquinolin-3-yl)-[1,2,4] triazolo[4,3-a]quinoxaline

• 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: 4-chloro-1-(2-chloro-6-methoxyquinolin-3-yl)-[1,2,4] triazolo[4,3-a]quinoxaline
• 英文别名: 4-Chloro-1-(2-chloro-6-methoxyquinolin-3-yl)-[1,2,4]triazolo[4,3-a]quinoxaline
• 化学式: C₁₉H₁₁Cl₂N₅O
• 分子量: 396.235
• InChiKey: ABGPUQXRCXUIFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4'-甲氧基乙酰苯胺 在 2,3-二氯-5,6-二氰基-1,4-苯醌 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 12.08h， 生成 4-chloro-1-(2-chloro-6-methoxyquinolin-3-yl)-[1,2,4] triazolo[4,3-a]quinoxaline
  参考文献：
  名称：

  Discovery of triazoloquinoxaline as novel STING agonists via structure-based virtual screening

  摘要：

  Stimulator of interferon genes (STING) is an endoplasmic reticulum adaptor facilitating innate immune signaling. Activation of STING leads to expression of interferons (IFNs) and pro-inflammatory cytokines which is associated with antiviral and antitumor responses. It is imperative to discovery potent compounds that precisely modulate STING. Herein, we describe the discovery of triazoloquinoxaline 1a as a novel STING agonist via Structure-based Virtual Screening. Specifically, biochemical and cell-based assays suggested that 1a stimulated concentration-dependently mRNA expression of IFNβ, CXCL-10 and IL-6. Furthermore, 1a significantly induced phosphorylation of STING, TANK-binding kinases1 (TBK1) and interferon regulatory factor 3 (IRF3), suggesting the activation of STING and its downstream TBK1-IRF3 signaling axis. In addition, 1a activated secretion of secreted alkaline phosphatase (SEAP) in dose-dependent manner and EC50 was 16.77 ± 3.814 μM, which is comparable with EC50 of 2'3'-cGAMP (9.212 ± 2.229 μM). These studies revealed that 1a is a promising STING agonist possessing the potential to be further developed for antiviral and antitumor treatment.

  DOI：

  10.1016/j.bioorg.2020.103958

文献信息

• A FACILE SYNTHESIS OF CHROMONYL & QUINOLINYL 1,2,4-s-TRIAZOLO [4,3-a] QUINOXALINES BY DEHYDROGENATIVE CYCLIZATION USING DDQ
  作者：G. Jagath Reddy、D. Latha、C. Thirupathaiah

  DOI：10.1515/hc.2003.9.3.243

  日期：2003.1
• Discovery of triazoloquinoxaline as novel STING agonists via structure-based virtual screening
  作者：Hui Hou、Ruirui Yang、Xiaohong Liu、Xiaolong Wu、Sulin Zhang、Kaixian Chen、Mingyue Zheng

  DOI：10.1016/j.bioorg.2020.103958

  日期：2020.7

  Stimulator of interferon genes (STING) is an endoplasmic reticulum adaptor facilitating innate immune signaling. Activation of STING leads to expression of interferons (IFNs) and pro-inflammatory cytokines which is associated with antiviral and antitumor responses. It is imperative to discovery potent compounds that precisely modulate STING. Herein, we describe the discovery of triazoloquinoxaline 1a as a novel STING agonist via Structure-based Virtual Screening. Specifically, biochemical and cell-based assays suggested that 1a stimulated concentration-dependently mRNA expression of IFNβ, CXCL-10 and IL-6. Furthermore, 1a significantly induced phosphorylation of STING, TANK-binding kinases1 (TBK1) and interferon regulatory factor 3 (IRF3), suggesting the activation of STING and its downstream TBK1-IRF3 signaling axis. In addition, 1a activated secretion of secreted alkaline phosphatase (SEAP) in dose-dependent manner and EC50 was 16.77 ± 3.814 μM, which is comparable with EC50 of 2'3'-cGAMP (9.212 ± 2.229 μM). These studies revealed that 1a is a promising STING agonist possessing the potential to be further developed for antiviral and antitumor treatment.