N-(4-cyanophenylmethyl)-4-[2-(1-methylethyl)phenyl]-1-piperazinehexanamide | 1052401-93-0

• 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: N-(4-cyanophenylmethyl)-4-[2-(1-methylethyl)phenyl]-1-piperazinehexanamide
• 英文别名: N-[(4-cyanophenyl)methyl]-6-[4-(2-propan-2-ylphenyl)piperazin-1-yl]hexanamide
• CAS: 1052401-93-0
• 化学式: C₂₇H₃₆N₄O
• 分子量: 432.609
• InChiKey: IJMJZSNLRMYGOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-bromo-N-(4-cyanophenylmethyl)hexanamide 、 1-(2-异丙基苯基)哌嗪 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以83%的产率得到N-(4-cyanophenylmethyl)-4-[2-(1-methylethyl)phenyl]-1-piperazinehexanamide
  参考文献：
  名称：

  Structural Modifications of N-(1,2,3,4-Tetrahydronaphthalen-1-yl)-4-Aryl-1-piperazinehexanamides: Influence on Lipophilicity and 5-HT₇ Receptor Activity. Part III

  摘要：

  Starting from the previously reported 5-HT7 receptor agents 4-7 with N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamide structure, the 1-(2-methylthiophenyl)-, 1-(2-diphenyl)-, 1-(2-isopropylphenyl)-, and 1-(2-methoxyphenyl)piperazine derivatives 8-31 were designed with the primary aim to obtain new compounds endowed with suitable physicochemical properties for rapid and extensive penetration into the brain. The affinities for 5-HT7, 5-HT1A, and D-2 receptors of compounds 8-31 were assessed, and several compounds displayed 5-HT7 receptor affinities in the nanomolar range. Among these, N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (25) showed high 5-HT7 receptor affinity (K-i = 0.58 nM), high selectivity over 5-HT1A and D-2 receptors (324- and 245-fold, respectively), and agonist properties (maximal effect = 82%, EC50 = 0.60 mu M). After intraperitoneal injection in mice, 25 rapidly reached the systemic circulation and entered the brain. Its brain concentration-time profile paralleled that in plasma, indicating that 25 rapidly and freely distributes across the blood-brain barrier. Compound 25 underwent N-dealkylation to the corresponding 1-arylpiperazine metabolite.

  DOI：

  10.1021/jm800615e

文献信息

• Structural Modifications of <i>N</i>-(1,2,3,4-Tetrahydronaphthalen-1-yl)-4-Aryl-1-piperazinehexanamides: Influence on Lipophilicity and 5-HT₇ Receptor Activity. Part III
  作者：Marcello Leopoldo、Enza Lacivita、Paola De Giorgio、Claudia Fracasso、Sara Guzzetti、Silvio Caccia、Marialessandra Contino、Nicola A. Colabufo、Francesco Berardi、Roberto Perrone

  DOI：10.1021/jm800615e

  日期：2008.9.25

  Starting from the previously reported 5-HT7 receptor agents 4-7 with N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamide structure, the 1-(2-methylthiophenyl)-, 1-(2-diphenyl)-, 1-(2-isopropylphenyl)-, and 1-(2-methoxyphenyl)piperazine derivatives 8-31 were designed with the primary aim to obtain new compounds endowed with suitable physicochemical properties for rapid and extensive penetration into the brain. The affinities for 5-HT7, 5-HT1A, and D-2 receptors of compounds 8-31 were assessed, and several compounds displayed 5-HT7 receptor affinities in the nanomolar range. Among these, N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (25) showed high 5-HT7 receptor affinity (K-i = 0.58 nM), high selectivity over 5-HT1A and D-2 receptors (324- and 245-fold, respectively), and agonist properties (maximal effect = 82%, EC50 = 0.60 mu M). After intraperitoneal injection in mice, 25 rapidly reached the systemic circulation and entered the brain. Its brain concentration-time profile paralleled that in plasma, indicating that 25 rapidly and freely distributes across the blood-brain barrier. Compound 25 underwent N-dealkylation to the corresponding 1-arylpiperazine metabolite.