(S)-2,3-dihydro-1,4-benzodioxine-2-(R)-ethanamine | 1020746-81-9

• 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-(R)-ethanamine
• 英文别名: (1R)-1-[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]ethanamine
• CAS: 1020746-81-9
• 化学式: C₁₀H₁₃NO₂
• 分子量: 179.219
• InChiKey: AANTWDPFFAREMQ-GMSGAONNSA-N

物化性质

• 沸点：
  273.8±19.0 °C(Predicted)
• 密度：
  1.136±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2,3-dihydro-1,4-benzodioxine-2-(R)-ethanamine 、 2,2-二苯基乙酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.08h， 生成 N-[(S)-2,3-dihydro-1,4-benzodioxine-2-(R)-ethyl]-2,2,-diphenylacetamide
  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：

  (R)-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 (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