3-[(1-benzylpiperidin-4-yl)methyl]benzo[d]oxazol-2(3H)-one | 1119185-05-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-[(1-benzylpiperidin-4-yl)methyl]benzo[d]oxazol-2(3H)-one
• 英文别名: 3-((1-benzylpiperidin-4-yl)methyl)benzo[d]oxazol-2(3H)-one；3-[(1-benzylpiperidin-4-yl)methyl]-1,3-benzoxazol-2-one
• CAS: 1119185-05-5
• 化学式: C₂₀H₂₂N₂O₂
• 分子量: 322.407
• InChiKey: CJLDVRVPMPWWTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-[(piperidin-4-yl)methyl]benzo[d]oxazol-2(3H )-one 、 氯化苄 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 5.0h， 以77%的产率得到3-[(1-benzylpiperidin-4-yl)methyl]benzo[d]oxazol-2(3H)-one
  参考文献：
  名称：

  Substituted benzo[d]oxazol-2(3H)-one derivatives with preference for the σ1 binding site☆

  摘要：

  We describe here the synthesis and the binding interaction with sigma(1) and sigma(2) receptors of a series of new benzo[d]oxazol-2(3H)-one derivatives variously substituted on the N-benzyl moiety. The results of binding studies confirm the notion that the benzoxazolone moiety confers preference towards sigma(1) sites and establish that the ability to bind to sigma(1), but not to sigma(2) receptors, is strongly affected by the kind and the position of the substituents introduced in the N-benzyl ring. In fact, compounds with substitutions in para-position with atoms of Cl, H or F or with a CH3 group exhibit a higher affinity for sigma(1) receptors than the corresponding ortho-substituted compounds. The highest affinity and selectivity, with K-i values of 0.1 and 427 nM for sigma(1) and sigma(2) receptors, respectively, and a corresponding K-i sigma(2)/K-i sigma(1) selectivity ratio of 4270 were found for the Cl-substituted compound.These results indicate that benzo[d]oxazol-2(3H)-one derivatives are among the most selective and sigma(1) receptor-preferring ligands currently available. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.03.011

文献信息

• COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE
  申请人：Catalano Susan M.

  公开号：US20140378460A1

  公开（公告）日：2014-12-25

  This invention relates to the use sigma-2 receptor antagonists, and of pharmaceutical compositions comprising such compounds, in methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology and more broadly treating with such compounds and compositions neurodegenerative diseases and disorders associated with Abeta pathology. This invention also relates to methods for screening compounds for activity in inhibiting cognitive decline on the basis of their ability to bind to a sigma-2 receptor.

  本发明涉及使用sigma-2受体拮抗剂及包含这种化合物的药物组合物，用于抑制神经元细胞中Abeta相关突触丢失或突触功能障碍，调节神经元细胞中Abeta相关的膜转运变化，以及治疗与Abeta病理相关的认知衰退，更广泛地使用这种化合物和组合物治疗与Abeta病理相关的神经退行性疾病和障碍。本发明还涉及通过它们与sigma-2受体结合的能力来筛选具有抑制认知衰退活性的化合物的方法。
• Substituted benzo[d]oxazol-2(3H)-one derivatives with preference for the σ1 binding site☆
  作者：Daniele Zampieri、Maria Grazia Mamolo、Erik Laurini、Caterina Zanette、Chiara Florio、Simona Collina、Daniela Rossi、Ornella Azzolina、Luciano Vio

  DOI：10.1016/j.ejmech.2008.03.011

  日期：2009.1

  We describe here the synthesis and the binding interaction with sigma(1) and sigma(2) receptors of a series of new benzo[d]oxazol-2(3H)-one derivatives variously substituted on the N-benzyl moiety. The results of binding studies confirm the notion that the benzoxazolone moiety confers preference towards sigma(1) sites and establish that the ability to bind to sigma(1), but not to sigma(2) receptors, is strongly affected by the kind and the position of the substituents introduced in the N-benzyl ring. In fact, compounds with substitutions in para-position with atoms of Cl, H or F or with a CH3 group exhibit a higher affinity for sigma(1) receptors than the corresponding ortho-substituted compounds. The highest affinity and selectivity, with K-i values of 0.1 and 427 nM for sigma(1) and sigma(2) receptors, respectively, and a corresponding K-i sigma(2)/K-i sigma(1) selectivity ratio of 4270 were found for the Cl-substituted compound.These results indicate that benzo[d]oxazol-2(3H)-one derivatives are among the most selective and sigma(1) receptor-preferring ligands currently available. (C) 2008 Elsevier Masson SAS. All rights reserved.