[4-(benzyloxy)-1,2,5-oxadiazol-3-yl]methanol | 1226869-68-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4-(benzyloxy)-1,2,5-oxadiazol-3-yl]methanol
• 英文别名: (4-Phenylmethoxy-1,2,5-oxadiazol-3-yl)methanol
• CAS: 1226869-68-6
• 化学式: C₁₀H₁₀N₂O₃
• 分子量: 206.201
• InChiKey: APULLFGUDUKBQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(benzyloxy)-1,2,5-oxadiazol-3-yl]methanol 在 偶氮二甲酸二异丙酯 、 水 、 三苯基膦 、 甲胺 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Heterocyclic ring cleavage upon collision-induced dissociation of deprotonated 3-hydroxy-1,2,5-oxadiazoles (3-hydroxyfurazans)

  摘要：

  对一系列 4-取代的 3-羟基呋喃进行了电喷雾离子化串联质谱分析。在低碰撞能量下，氧异氰酸酯（[O=C=N-O]-，m/z 58）形成为每个去质子化 3-羟基呋喃的主要产物离子，表明杂环被裂解。密度泛函计算证实了这一特征碎裂过程的简易能量学原理。

  DOI：

  10.1002/jms.3724
• 作为产物：
  描述：

  methyl 4-(benzyloxy)-1,2,5-oxadiazole-3-carboxylate 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 以73%的产率得到[4-(benzyloxy)-1,2,5-oxadiazol-3-yl]methanol
  参考文献：
  名称：

  4-Hydroxy-1,2,5-oxadiazol-3-yl Moiety as Bioisoster of the Carboxy Function. Synthesis, Ionization Constants, and Molecular Pharmacological Characterization at Ionotropic Glutamate Receptors of Compounds Related to Glutamate and Its Homologues

  摘要：

  In order to investigate the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as a carboxylic acid bioisoster at ionotropic glutamate receptors (iGluRs), a series of acidic alpha-aminocarboxylic acids in which the distal carboxy group was replaced by the 4-hydroxy-1,2,5-oxadiazol-3-yl group was synthesized. Ionization constants were determined. All target compounds, except the Asp analogue 12, were resolved using chiral HPLC. Whereas 12 showed good affinity exclusively at NMDA receptors, the Glu analogue, (+)-10, was an unselective, though potent AMPA receptor preferring agonist (EC(50) = 10 mu M at iGluR2) showing only low stereoselectivity. The two higher Glu homologues, (+)-15 and (+)-18, turned out to be weak agonists at iGluR2 as well as weak antagonists at NR1/NR2A, whereas the corresponding (-)-isomers were selective NR1/NR2A antagonists with somewhat higher potency. The results proved the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety to be a useful bioisoster at all three classes of iGluRs, capable of being integrated into agonists as well as antagonists.

  DOI：

  10.1021/jm1001452

文献信息

• 4-Hydroxy-1,2,5-oxadiazol-3-yl Moiety as Bioisoster of the Carboxy Function. Synthesis, Ionization Constants, and Molecular Pharmacological Characterization at Ionotropic Glutamate Receptors of Compounds Related to Glutamate and Its Homologues
  作者：Marco L. Lolli、Cecilia Giordano、Darryl S. Pickering、Barbara Rolando、Kasper B. Hansen、Antonio Foti、Alberto Contreras-Sanz、Ahmad Amir、Roberta Fruttero、Alberto Gasco、Birgitte Nielsen、Tommy N. Johansen

  DOI：10.1021/jm1001452

  日期：2010.5.27

  In order to investigate the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as a carboxylic acid bioisoster at ionotropic glutamate receptors (iGluRs), a series of acidic alpha-aminocarboxylic acids in which the distal carboxy group was replaced by the 4-hydroxy-1,2,5-oxadiazol-3-yl group was synthesized. Ionization constants were determined. All target compounds, except the Asp analogue 12, were resolved using chiral HPLC. Whereas 12 showed good affinity exclusively at NMDA receptors, the Glu analogue, (+)-10, was an unselective, though potent AMPA receptor preferring agonist (EC(50) = 10 mu M at iGluR2) showing only low stereoselectivity. The two higher Glu homologues, (+)-15 and (+)-18, turned out to be weak agonists at iGluR2 as well as weak antagonists at NR1/NR2A, whereas the corresponding (-)-isomers were selective NR1/NR2A antagonists with somewhat higher potency. The results proved the 4-hydroxy-1,2,5-oxadiazol-3-yl moiety to be a useful bioisoster at all three classes of iGluRs, capable of being integrated into agonists as well as antagonists.
• Heterocyclic ring cleavage upon collision-induced dissociation of deprotonated 3-hydroxy-1,2,5-oxadiazoles (3-hydroxyfurazans)
  作者：J. Stuart Grossert、Agnese C. Pippione、Donatella Boschi、Marco L. Lolli、Robert L. White

  DOI：10.1002/jms.3724

  日期：2015.12

  A series of 4-substituted 3-hydroxyfurazans were subjected to electrospray ionization tandem mass spectrometry. At low collision energy, oxyisocyanate ([O=C=N–O]−, m/z 58) was formed as the predominant product ion from each deprotonated 3-hydroxyfurazan, indicating cleavage of the heterocyclic ring. The facile energetics of this characteristic fragmentation process was confirmed by density functional computations.

  对一系列 4-取代的 3-羟基呋喃进行了电喷雾离子化串联质谱分析。在低碰撞能量下，氧异氰酸酯（[O=C=N-O]-，m/z 58）形成为每个去质子化 3-羟基呋喃的主要产物离子，表明杂环被裂解。密度泛函计算证实了这一特征碎裂过程的简易能量学原理。