1-benzyl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-benzyl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazine
• 英文别名: 1-Benzyl-4-[3-(3,4-dihydro-naphthalen-1-yl)-propyl]-piperazine；1-benzyl-4-[3-(3,4-dihydronaphthalen-1-yl)propyl]piperazine
• 化学式: C₂₄H₃₀N₂
• 分子量: 346.516
• InChiKey: BURLNZFZEWVOBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-苄基哌嗪 、 4-(3-bromo-n-propyl)-1,2-dihydronaphthalene 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以95%的产率得到1-benzyl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazine
  参考文献：
  名称：

  New σ and 5-HT_1A Receptor Ligands:  ω-(Tetralin-1-yl)-n-alkylamine Derivatives

  摘要：

  Two series of compounds that are structurally related to benzomorphans, derived by structural modification of arylpiperazines with high 5-HT1A affinity and moderate a affinity, were prepared in order to increase a affinity and selectivity. All new compounds are N-substituted-omega-(1,2,3,4-tetrahydronaphthalen-1-yl)- or -omega-(1,2-dihydronaphthalen-4-yl)-n-alkylamines with, in some cases, a methoxy group on the tetralin moiety. They were tested in radioligand binding assays on sigma ([H-3]DTG and [H-3]-(+)-pentazocine), D-2 dopaminergic, 5-HT1A and 5-HT2 serotonergic, and PCP (phencyclidine) receptors. A first set of compounds bearing a 4-(1-substituted)piperazine moiety as terminal fragment on the alkyl chain showed moderate to high sigma affinity (K-i = 5.3-139 nM), the most active and selective being 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-proyl]piperazine (14), with probable pronounced alpha(2) affinity (K-i = 5.3 nM on [H-3]DTG and K-i = 71 nM on [H-3]-(+)-pentazocine). Moreover, compound 13, a 1-benzylpiperazine analogue of 14, preserved a dual high 5-HT1A and sigma affinity (K-i = 3.6 nM on [H-3]-5-HT and K-i = 7.0 nM on [H-3]DTG). The second set of compounds includes some N-phenylalkyl derivatives of 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propylamine that can be considered. to be open-chain derivatives of 4-substituted-1-arylpiperazines. Among these compounds that had a lower activity toward sigma binding sites, a high 5-HT1A affinity was found for the N-(3-phenylpropyl) derivative 21 (K-i = 4.4 nM) which demonstrated very good selectivity.

  DOI：

  10.1021/jm950409c

文献信息

• New σ and 5-HT_1A Receptor Ligands:  ω-(Tetralin-1-yl)-<i>n</i>-alkylamine Derivatives
  作者：Francesco Berardi、Nicola A. Colabufo、Giuseppe Giudice、Roberto Perrone、Vincenzo Tortorella、Stefano Govoni、Laura Lucchi

  DOI：10.1021/jm950409c

  日期：1996.1.1

  Two series of compounds that are structurally related to benzomorphans, derived by structural modification of arylpiperazines with high 5-HT1A affinity and moderate a affinity, were prepared in order to increase a affinity and selectivity. All new compounds are N-substituted-omega-(1,2,3,4-tetrahydronaphthalen-1-yl)- or -omega-(1,2-dihydronaphthalen-4-yl)-n-alkylamines with, in some cases, a methoxy group on the tetralin moiety. They were tested in radioligand binding assays on sigma ([H-3]DTG and [H-3]-(+)-pentazocine), D-2 dopaminergic, 5-HT1A and 5-HT2 serotonergic, and PCP (phencyclidine) receptors. A first set of compounds bearing a 4-(1-substituted)piperazine moiety as terminal fragment on the alkyl chain showed moderate to high sigma affinity (K-i = 5.3-139 nM), the most active and selective being 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-proyl]piperazine (14), with probable pronounced alpha(2) affinity (K-i = 5.3 nM on [H-3]DTG and K-i = 71 nM on [H-3]-(+)-pentazocine). Moreover, compound 13, a 1-benzylpiperazine analogue of 14, preserved a dual high 5-HT1A and sigma affinity (K-i = 3.6 nM on [H-3]-5-HT and K-i = 7.0 nM on [H-3]DTG). The second set of compounds includes some N-phenylalkyl derivatives of 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propylamine that can be considered. to be open-chain derivatives of 4-substituted-1-arylpiperazines. Among these compounds that had a lower activity toward sigma binding sites, a high 5-HT1A affinity was found for the N-(3-phenylpropyl) derivative 21 (K-i = 4.4 nM) which demonstrated very good selectivity.