3-((1-ethyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)amino)phenol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-((1-ethyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)amino)phenol
• 英文别名: 3-({1-Ethyl-[1,2,4]triazolo[4,3-A]quinoxalin-4-YL}amino)phenol；3-[(1-ethyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)amino]phenol
• 化学式: C₁₇H₁₅N₅O
• mdl: MFCD14925003
• 分子量: 305.339
• InChiKey: YLHFUEITIFOPAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  75.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3-二氯喹喔啉 在 一水合肼 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 16.0h， 生成 3-((1-ethyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)amino)phenol
  参考文献：
  名称：

  Introducing structure-based three-dimensional pharmacophore models for accelerating the discovery of selective BRD9 binders

  摘要：

  A well-structured in silico workflow is here reported for disclosing structure-based pharmacophore models against bromodomain-containing protein 9 (BRD9), accelerating virtual screening campaigns and facilitating the identification of novel binders. Specifically, starting from 23 known ligands co-crystallized with BRD9, three-dimensional pharmacophore models, namely placed in a reference protein structure, were developed. Specifically, we here introduce a fragment-related pharmacophore model, useful for the identification of new promising small chemical probes targeting the protein region responsible of the acetyllysine recognition, and two further pharmacophore models useful for the selection of compounds featuring drug-like properties. A pharmacophore-driven virtual screening campaign was then performed to facilitate the selection of new selective BRD9 ligands, starting from a large library of commercially available molecules. The identification of a promising BRD9 binder (7) prompted us to re-iterate this computational workflow on a second focused in-house built library of synthesizable compounds and, eventually, three further novel BRD9 binders were disclosed (8-10). Moreover, all these compounds were tested among a panel comprising other nine bromodomains, showing a high selectivity for BRD9. Preclinical bioscreens for potential anticancer activity highlighted compound 7 as that showing the most promising biological effects, proving the reliability of this in silico pipeline and confirming the applicability of the here introduced structure-based three-dimensional (3D) pharmacophore models as straightforward tools for the selection of new BRD9 ligands.

  DOI：

  10.1016/j.bioorg.2021.105480

文献信息

• Introducing structure-based three-dimensional pharmacophore models for accelerating the discovery of selective BRD9 binders
  作者：Martina Pierri、Erica Gazzillo、Maria Giovanna Chini、Maria Grazia Ferraro、Marialuisa Piccolo、Francesco Maione、Carlo Irace、Giuseppe Bifulco、Ines Bruno、Stefania Terracciano、Gianluigi Lauro

  DOI：10.1016/j.bioorg.2021.105480

  日期：2022.1

  A well-structured in silico workflow is here reported for disclosing structure-based pharmacophore models against bromodomain-containing protein 9 (BRD9), accelerating virtual screening campaigns and facilitating the identification of novel binders. Specifically, starting from 23 known ligands co-crystallized with BRD9, three-dimensional pharmacophore models, namely placed in a reference protein structure, were developed. Specifically, we here introduce a fragment-related pharmacophore model, useful for the identification of new promising small chemical probes targeting the protein region responsible of the acetyllysine recognition, and two further pharmacophore models useful for the selection of compounds featuring drug-like properties. A pharmacophore-driven virtual screening campaign was then performed to facilitate the selection of new selective BRD9 ligands, starting from a large library of commercially available molecules. The identification of a promising BRD9 binder (7) prompted us to re-iterate this computational workflow on a second focused in-house built library of synthesizable compounds and, eventually, three further novel BRD9 binders were disclosed (8-10). Moreover, all these compounds were tested among a panel comprising other nine bromodomains, showing a high selectivity for BRD9. Preclinical bioscreens for potential anticancer activity highlighted compound 7 as that showing the most promising biological effects, proving the reliability of this in silico pipeline and confirming the applicability of the here introduced structure-based three-dimensional (3D) pharmacophore models as straightforward tools for the selection of new BRD9 ligands.