1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-n-decylpiperazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-n-decylpiperazine
• 英文别名: 1-Decyl-4-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-piperazine；1-decyl-4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine
• 化学式: C₂₂H₃₆N₂O₂
• 分子量: 360.54
• InChiKey: ZWPCABJDUWYWJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  24.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2,3-二氢-1,4-苯并二烷-5-基)哌嗪盐酸盐 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 2.0h， 生成 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-n-decylpiperazine
  参考文献：
  名称：

  Structure-affinity relationship studies on 5-HT1A receptor ligands. 1. Heterobicyclic phenylpiperazines with N4-alkyl substituents

  摘要：

  Structure-affinity relationship (SAR) studies for 5-HT1A receptor site are presented for two series of heterobicyclic phenylpiperazines with N4-alkyl substituents: 4-alkyl derivatives of 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine (3) and 1-(benzo[b]furan-7-yl)piperazine (4). The linear and branched hydrocarbon chain derivatives up to n-decyl were synthesized and evaluated for their ability to displace [H-3]-2-(di-n-propylamino)-8-hydroxytetralin from its specific binding sites in rat frontal cortex homogenates. All compounds displayed a nanomolar affinity for the 5-HT1A receptor. In both series the N-ethyl and N-n-propyl substituted derivatives have similar affinities, being slightly but statistically significantly less active than the N-methyl-substituted derivatives. Elongation of the hydrocarbon chain increases the affinity for the central 5-HT1A receptor site, reaching a local maximum for the N-n-hexyl-substituted phenylpiperazines 23 (K(i) = 0.50 nM) and 39 (K(i) = 0.54 nM). Assuming that the arylpiperazine derivatives at the 5-HT1A binding site are in the ionic state, ionization constants were determined in order to evaluate the use of the local inhibition constant, K(i)+, as a more convenient parameter to study the structure-affinity relationships. However, the K(i)+ could not account for the specific N4-substituent effects found.

  DOI：

  10.1021/jm00071a006

文献信息

• Structure-affinity relationship studies on 5-HT1A receptor ligands. 1. Heterobicyclic phenylpiperazines with N4-alkyl substituents
  作者：Bart J. van Steen、Ineke van Wijngaarden、Martin T. M. Tulp、Willem Soudijn

  DOI：10.1021/jm00071a006

  日期：1993.9

  Structure-affinity relationship (SAR) studies for 5-HT1A receptor site are presented for two series of heterobicyclic phenylpiperazines with N4-alkyl substituents: 4-alkyl derivatives of 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine (3) and 1-(benzo[b]furan-7-yl)piperazine (4). The linear and branched hydrocarbon chain derivatives up to n-decyl were synthesized and evaluated for their ability to displace [H-3]-2-(di-n-propylamino)-8-hydroxytetralin from its specific binding sites in rat frontal cortex homogenates. All compounds displayed a nanomolar affinity for the 5-HT1A receptor. In both series the N-ethyl and N-n-propyl substituted derivatives have similar affinities, being slightly but statistically significantly less active than the N-methyl-substituted derivatives. Elongation of the hydrocarbon chain increases the affinity for the central 5-HT1A receptor site, reaching a local maximum for the N-n-hexyl-substituted phenylpiperazines 23 (K(i) = 0.50 nM) and 39 (K(i) = 0.54 nM). Assuming that the arylpiperazine derivatives at the 5-HT1A binding site are in the ionic state, ionization constants were determined in order to evaluate the use of the local inhibition constant, K(i)+, as a more convenient parameter to study the structure-affinity relationships. However, the K(i)+ could not account for the specific N4-substituent effects found.