(S)-2,3-dihydro-1,4-benzodioxine-2-methyl ketone | 1092659-03-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (S)-2,3-dihydro-1,4-benzodioxine-2-methyl ketone
• 英文别名: (S)‐2‐acetyl‐1,4‐benzodioxane；1-[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]ethanone
• CAS: 1092659-03-4
• 化学式: C₁₀H₁₀O₃
• 分子量: 178.188
• InChiKey: KVCWAZWJLMNADA-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2,3-dihydro-1,4-benzodioxine-2-methyl ketone 在 titanium(IV) isopropylate 、 氨 、 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 (R)-2,3-dihydro-1,4-benzodioxine-2-(S)-ethanamine 、 (R)-2,3-dihydro-1,4-benzodioxine-2-(R)-ethanamine 、 (S)-2,3-dihydro-1,4-benzodioxine-2-(S)-ethanamine 、 (S)-2,3-dihydro-1,4-benzodioxine-2-(R)-ethanamine
  参考文献：
  名称：

  A Virtual Screen for Diverse Ligands: Discovery of Selective G Protein-Coupled Receptor Antagonists

  摘要：

  Virtual screening has become a major focus of bioactive small molecule lead identification, and reports of agonists and antagonists discovered via virtual methods are becoming more frequent. G protein-coupled receptors (GPCRs) are the one class of protein targets for which success with this approach has been limited. This is likely due to the paucity of detailed experimental information describing GPCR structure and the intrinsic function-associated structural flexibility of GPCRs which present major challenges in the application of receptor-based virtual screening. Here we describe an in silico methodology that diminishes the effects of structural uncertainty, allowing for more inclusive representation of a potential docking interaction with exogenous ligands. Using this approach, we screened one million compounds from a virtual database, and a diverse subgroup of 100 compounds was selected, leading to experimental identification of five structurally diverse antagonists of the thyrotropin-releasing hormone receptors (TRH-R1 and TRH-R2). The chirality of the most potent chemotype was demonstrated to be important in,its binding affinity to TRH receptors; the most potent stereoisomer was noted to have a 13-fold selectivity for TRH-R1 over TRH-R2. A comprehensive mutational analysis of key amino acid residues that form the putative binding pocket of TRH receptors further verified the binding modality of these small molecule antagonists. The described virtual screening approach may prove applicable in the search for novel small molecule agonists and antagonists of other GPCRs.

  DOI：

  10.1021/ja077620l
• 作为产物：
  描述：

  (2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(1H-imidazol-1-yl)methanone 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 18.5h， 生成 (S)-2,3-dihydro-1,4-benzodioxine-2-methyl ketone
  参考文献：
  名称：

  反应条件如何影响2-取代-1,4-苯并二恶烷衍生物的对映体纯合成？

  摘要：

  几种具有生物活性的化合物在结构上包括对映体2-取代-1,4-苯并二恶烷骨架。因此，影响涉及大多数常见化学反应物的反应的直接外消旋作用是至关重要的问题。因此，必须开发一种不影响对映体过量的完全立体控制的合成路线。建立可靠的手性HPLC方法，使其能够追踪反应并改善合成性能也很重要。在这里，我们报告了两种不同合成子的手性研究，我们专门评估了可以运行的合成途径以提供它们，从而避免了通常在碱性条件下可能发生的外消旋过程。此外，我们开发了独特的手性HPLC方法来拆分对映体，

  DOI：

  10.1002/chir.22968

文献信息

• How do reaction conditions affect the enantiopure synthesis of 2-substituted-1,4-benzodioxane derivatives?
  作者：Valentina Straniero、Andrea Casiraghi、Laura Fumagalli、Ermanno Valoti

  DOI：10.1002/chir.22968

  日期：2018.7

  biologically active compounds structurally include the enantiopure 2‐substituted‐1,4‐benzodioxane scaffold. The straightforward racemization that affects reactions involving most of the common chemical reactives is thus a crucial issue. The developing of a completely stereo‐controlled synthetic route that does not affect the enantiomeric excess is consequently mandatory. It is also important to set up a reliable

  几种具有生物活性的化合物在结构上包括对映体2-取代-1,4-苯并二恶烷骨架。因此，影响涉及大多数常见化学反应物的反应的直接外消旋作用是至关重要的问题。因此，必须开发一种不影响对映体过量的完全立体控制的合成路线。建立可靠的手性HPLC方法，使其能够追踪反应并改善合成性能也很重要。在这里，我们报告了两种不同合成子的手性研究，我们专门评估了可以运行的合成途径以提供它们，从而避免了通常在碱性条件下可能发生的外消旋过程。此外，我们开发了独特的手性HPLC方法来拆分对映体，
• A Virtual Screen for Diverse Ligands: Discovery of Selective G Protein-Coupled Receptor Antagonists
  作者：Stanislav Engel、Amanda P. Skoumbourdis、John Childress、Susanne Neumann、Jeffrey R. Deschamps、Craig J. Thomas、Anny-Odile Colson、Stefano Costanzi、Marvin C. Gershengorn

  DOI：10.1021/ja077620l

  日期：2008.4.1

  Virtual screening has become a major focus of bioactive small molecule lead identification, and reports of agonists and antagonists discovered via virtual methods are becoming more frequent. G protein-coupled receptors (GPCRs) are the one class of protein targets for which success with this approach has been limited. This is likely due to the paucity of detailed experimental information describing GPCR structure and the intrinsic function-associated structural flexibility of GPCRs which present major challenges in the application of receptor-based virtual screening. Here we describe an in silico methodology that diminishes the effects of structural uncertainty, allowing for more inclusive representation of a potential docking interaction with exogenous ligands. Using this approach, we screened one million compounds from a virtual database, and a diverse subgroup of 100 compounds was selected, leading to experimental identification of five structurally diverse antagonists of the thyrotropin-releasing hormone receptors (TRH-R1 and TRH-R2). The chirality of the most potent chemotype was demonstrated to be important in,its binding affinity to TRH receptors; the most potent stereoisomer was noted to have a 13-fold selectivity for TRH-R1 over TRH-R2. A comprehensive mutational analysis of key amino acid residues that form the putative binding pocket of TRH receptors further verified the binding modality of these small molecule antagonists. The described virtual screening approach may prove applicable in the search for novel small molecule agonists and antagonists of other GPCRs.