2-chloro-6-(1,3-dioxolan-2-yl)quinoline | 791626-62-5

• 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: 2-chloro-6-(1,3-dioxolan-2-yl)quinoline
• CAS: 791626-62-5
• 化学式: C₁₂H₁₀ClNO₂
• 分子量: 235.67
• InChiKey: KIUPMJLVCQCDOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-6-(1,3-dioxolan-2-yl)quinoline 在 lithium aluminium tetrahydride 、 三氯化铝 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 生成 2-amino-6-[(2-hydroxyethoxy)methyl]quinoline
  参考文献：
  名称：

  5-，6-和7-取代的2-氨基喹啉作为SH3结构域配体的合成。

  摘要：

  Src同源性3（SH3）域是小的蛋白质-蛋白质相互作用域，介导一系列重要的生物学过程，被认为是治疗剂开发的重要靶标。我们一直在开发2-氨基喹啉作为SH3结构域的配体-迄今为止，仅有报道的SH3结构域完全小分子配体的例子。迄今为止确定的最高亲和力的2-氨基喹啉是6-取代的化合物。在本文中，提出了几种新的2-氨基喹啉的合成方法，包括用于Tec SH3结构域配体结合研究的5-，6-和7-取代的化合物。作为综合调查的一部分，探索了用于合成2-氨基喹啉的不同方法的实用性，并确定了用于合成具有多种功能的2-氨基喹啉的潜在有效方法。在制备的化合物中，5-取代的2-氨基喹啉通常以与未取代的2-氨基喹啉相似的亲和力结合，而7-取代的化合物通常以与未取代的2-氨基喹啉相似或更低的亲和力结合。然而，6-取代的2-氨基喹啉通常以比未取代的2-氨基喹啉更高的亲和力结合。另外，还测试了一种6-取代的-N-苄基化的2-

  DOI：

  10.1039/b504498g
• 作为产物：
  描述：

  2-氯-6-甲基喹啉 在 N-溴代丁二酰亚胺(NBS) 、 对甲苯磺酸 、 过氧化苯甲酰 作用下， 以 苯 为溶剂， 反应 10.0h， 生成 2-chloro-6-(1,3-dioxolan-2-yl)quinoline
  参考文献：
  名称：

  Identification and Specificity Studies of Small-Molecule Ligands for SH3 Protein Domains

  摘要：

  The Src Homology 3 (SH3) domains are small protein-protein interaction domains that bind proline-rich sequences and mediate a wide range of cell-signaling and other important biological processes. Since deregulated signaling pathways form the basis of many human diseases, the SH3 domains have been attractive targets for novel therapeutics. High-affinity ligands for SH3 domains have been designed; however, these have all been peptide-based and no examples of entirely nonpeptide SH3 ligands have previously been reported. Using the mouse Tec Kinase SH3 domain as a model system for structure-based ligand design, we have identified several simple heterocyclic compounds that selectively bind to the Tec SH3 domain. Using a combination of nuclear magnetic resonance chemical shift perturbation, structure-activity relationships, and site-directed mutagenesis, the binding of these compounds at the proline-rich peptide-binding site has been characterized. The most potent of these, 2-aminoquinoline, bound with K-d = 125 muM and was able to compete for binding with a proline-rich peptide. Synthesis of 6-substitued-2-aminoquinolines resulted in ligands with up to 6-fold improved affinity over 2-aminoquinoline and enhanced specificity for the Tec SH3 domain. Therefore, 2-aminoquinolines may potentially be useful for the development of high affinity small molecule ligands for SH3 domains.

  DOI：

  10.1021/jm049533z

文献信息

• Identification and Specificity Studies of Small-Molecule Ligands for SH3 Protein Domains
  作者：Steven R. Inglis、Cvetan Stojkoski、Kim M. Branson、Jacquie F. Cawthray、Daniel Fritz、Emma Wiadrowski、Simon M. Pyke、Grant W. Booker

  DOI：10.1021/jm049533z

  日期：2004.10.1

  The Src Homology 3 (SH3) domains are small protein-protein interaction domains that bind proline-rich sequences and mediate a wide range of cell-signaling and other important biological processes. Since deregulated signaling pathways form the basis of many human diseases, the SH3 domains have been attractive targets for novel therapeutics. High-affinity ligands for SH3 domains have been designed; however, these have all been peptide-based and no examples of entirely nonpeptide SH3 ligands have previously been reported. Using the mouse Tec Kinase SH3 domain as a model system for structure-based ligand design, we have identified several simple heterocyclic compounds that selectively bind to the Tec SH3 domain. Using a combination of nuclear magnetic resonance chemical shift perturbation, structure-activity relationships, and site-directed mutagenesis, the binding of these compounds at the proline-rich peptide-binding site has been characterized. The most potent of these, 2-aminoquinoline, bound with K-d = 125 muM and was able to compete for binding with a proline-rich peptide. Synthesis of 6-substitued-2-aminoquinolines resulted in ligands with up to 6-fold improved affinity over 2-aminoquinoline and enhanced specificity for the Tec SH3 domain. Therefore, 2-aminoquinolines may potentially be useful for the development of high affinity small molecule ligands for SH3 domains.
• Synthesis of 5-, 6- and 7-substituted-2-aminoquinolines as SH3 domain ligands
  作者：Steven Inglis、Rhiannon Jones、Daniel Fritz、Cvetan Stojkoski、Grant Booker、Simon Pyke

  DOI：10.1039/b504498g

  日期：——

  affinity 2-aminoquinolines so far identified are 6-substituted compounds. In this article, the synthesis of several new 2-aminoquinolines, including 5-, 6- and 7-substituted compounds, for Tec SH3 domain ligand binding studies is presented. As a part of the synthetic investigation, the utility of different methods for the synthesis of 2-aminoquinolines was explored and potentially powerful methods were

  Src同源性3（SH3）域是小的蛋白质-蛋白质相互作用域，介导一系列重要的生物学过程，被认为是治疗剂开发的重要靶标。我们一直在开发2-氨基喹啉作为SH3结构域的配体-迄今为止，仅有报道的SH3结构域完全小分子配体的例子。迄今为止确定的最高亲和力的2-氨基喹啉是6-取代的化合物。在本文中，提出了几种新的2-氨基喹啉的合成方法，包括用于Tec SH3结构域配体结合研究的5-，6-和7-取代的化合物。作为综合调查的一部分，探索了用于合成2-氨基喹啉的不同方法的实用性，并确定了用于合成具有多种功能的2-氨基喹啉的潜在有效方法。在制备的化合物中，5-取代的2-氨基喹啉通常以与未取代的2-氨基喹啉相似的亲和力结合，而7-取代的化合物通常以与未取代的2-氨基喹啉相似或更低的亲和力结合。然而，6-取代的2-氨基喹啉通常以比未取代的2-氨基喹啉更高的亲和力结合。另外，还测试了一种6-取代的-N-苄基化的2-