2-[4-(benzyloxy)phenyl]ethyl 4-phenylbutyl ether | 212838-79-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-[4-(benzyloxy)phenyl]ethyl 4-phenylbutyl ether
• 英文别名: 1-[2-(4-Phenylbutoxy)ethyl]-4-(phenylmethoxy)benzene；1-[2-(4-phenylbutoxy)ethyl]-4-phenylmethoxybenzene
• CAS: 212838-79-4
• 化学式: C₂₅H₂₈O₂
• 分子量: 360.496
• InChiKey: PUCDDCXTZSGRCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[4-(benzyloxy)phenyl]ethyl 4-phenylbutyl ether 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以85%的产率得到2-(4-hydroxyphenyl)ethyl 4-phenylbutyl ether
  参考文献：
  名称：

  Structure−Activity Relationships for a Series of Bis(phenylalkyl)amines:  Potent Subtype-Selective Inhibitors of N-Methyl-d-aspartate Receptors

  摘要：

  A series of bis(phenylalkyl)amines, structural analogues of ifenprodil and nylidrin, were synthesized and tested for antagonism of N-methyl-D-aspartate (NMDA) receptors. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The bis(phenylalkyl)amines were selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, the most potent of these, N-[2-(4-hydroxyphenyl)ethyl]-5-phenylpentylamine hydrochloride (20), has an IC50 value of 8 nM and > 1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. The structure-activity relationship of the bis(phenylalkyl)amine series indicates that the piperidine ring and alkyl chain substitutions common to NR2B-selective antagonists such as ifenprodil, CP 101,606, and Ro 25-6981 are not necessary to generate potent and selective ligands. The primary determinants of potency are the phenolic OH group, acting as a hydrogen bond donor, the distance between the two rings, and an electrostatic interaction between the receptor and the basic nitrogen atom. This study provides a framework for designing structurally novel NR2B-selective antagonists which may be useful for treatment of a variety of neurological disorders.

  DOI：

  10.1021/jm980235+
• 作为产物：
  描述：

  2-(4-苯甲氧基苯基)乙醇 、 4-phenylbutyl 4-methylbenzenesulfonate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以93%的产率得到2-[4-(benzyloxy)phenyl]ethyl 4-phenylbutyl ether
  参考文献：
  名称：

  Structure−Activity Relationships for a Series of Bis(phenylalkyl)amines:  Potent Subtype-Selective Inhibitors of N-Methyl-d-aspartate Receptors

  摘要：

  A series of bis(phenylalkyl)amines, structural analogues of ifenprodil and nylidrin, were synthesized and tested for antagonism of N-methyl-D-aspartate (NMDA) receptors. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The bis(phenylalkyl)amines were selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, the most potent of these, N-[2-(4-hydroxyphenyl)ethyl]-5-phenylpentylamine hydrochloride (20), has an IC50 value of 8 nM and > 1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. The structure-activity relationship of the bis(phenylalkyl)amine series indicates that the piperidine ring and alkyl chain substitutions common to NR2B-selective antagonists such as ifenprodil, CP 101,606, and Ro 25-6981 are not necessary to generate potent and selective ligands. The primary determinants of potency are the phenolic OH group, acting as a hydrogen bond donor, the distance between the two rings, and an electrostatic interaction between the receptor and the basic nitrogen atom. This study provides a framework for designing structurally novel NR2B-selective antagonists which may be useful for treatment of a variety of neurological disorders.

  DOI：

  10.1021/jm980235+

文献信息

• Structure−Activity Relationships for a Series of Bis(phenylalkyl)amines:  Potent Subtype-Selective Inhibitors of <i>N</i>-Methyl-<scp>d</scp>-aspartate Receptors
  作者：Amir P. Tamiz、Edward R. Whittemore、Zhang-Lin Zhou、Jin-Cheng Huang、John A. Drewe、Jie-Cheng Chen、Sui-Xiong Cai、Eckard Weber、Richard M. Woodward、John F. W. Keana

  DOI：10.1021/jm980235+

  日期：1998.8.1

  A series of bis(phenylalkyl)amines, structural analogues of ifenprodil and nylidrin, were synthesized and tested for antagonism of N-methyl-D-aspartate (NMDA) receptors. Potency and subunit selectivity were assayed by electrical recordings in Xenopus oocytes expressing three binary combinations of cloned rat NMDA receptor subunits: NR1A expressed in combination with either NR2A, NR2B, or NR2C. The bis(phenylalkyl)amines were selective antagonists of NR1A/2B receptors. Assayed under steady-state conditions, the most potent of these, N-[2-(4-hydroxyphenyl)ethyl]-5-phenylpentylamine hydrochloride (20), has an IC50 value of 8 nM and > 1000-fold selectivity with respect to NR1A/2A and NR1A/2C receptors. The structure-activity relationship of the bis(phenylalkyl)amine series indicates that the piperidine ring and alkyl chain substitutions common to NR2B-selective antagonists such as ifenprodil, CP 101,606, and Ro 25-6981 are not necessary to generate potent and selective ligands. The primary determinants of potency are the phenolic OH group, acting as a hydrogen bond donor, the distance between the two rings, and an electrostatic interaction between the receptor and the basic nitrogen atom. This study provides a framework for designing structurally novel NR2B-selective antagonists which may be useful for treatment of a variety of neurological disorders.