1,2,3,4-tetrahydro-N-[3-[6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]propyl]-5-methoxynaphthalene-1-carboxamide | 1335092-95-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1,2,3,4-tetrahydro-N-[3-[6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]propyl]-5-methoxynaphthalene-1-carboxamide
• 英文别名: N-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)propyl]-5-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxamide
• CAS: 1335092-95-9
• 化学式: C₂₆H₃₄N₂O₄
• 分子量: 438.567
• InChiKey: FMCHNPVKNXRBMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  60
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6,7-二甲氧基-1,2,3,4-四氢异喹啉 在 dimethyl sulfide borane 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 1,2,3,4-tetrahydro-N-[3-[6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]propyl]-5-methoxynaphthalene-1-carboxamide
  参考文献：
  名称：

  Arylamides hybrids of two high-affinity σ2 receptor ligands as tools for the development of PET radiotracers

  摘要：

  1-Cyclohexy1-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) and 2-Methoxy-5-methyl-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)butyl]benzamide 2 (RHM-1) represent leads for tumor diagnosis, given their high affinity at sigma(2) receptors. With the purpose of obtaining good candidates for sigma(2) PET tracers development, hybrid structures between 1 and 2 were designed. Excellent sigma(1)/sigma(2) selectivities were reached when 6,7-dimethoxytetrahydroisoquinoline was linked to an o-methoxy substituted arylamide (11a, 12a, 15a). and for these benzamides an intramolecular H-bond in the active conformation at the sigma sites, was hypothesized. However these excellent sigma(2) ligands were accompanied by interaction with P-gp. which may limit their use as sigma(2) receptor PET agents when tumors overexpress P-gp. Compound 15a whose P-gp interaction was just moderate represents an interesting tool for the development of sigma(2) PET tracers useful in tumors overexpressing P-gp. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.057

文献信息

• Arylamides hybrids of two high-affinity σ2 receptor ligands as tools for the development of PET radiotracers
  作者：Carmen Abate、Savina Ferorelli、Marialessandra Contino、Roberta Marottoli、Nicola Antonio Colabufo、Roberto Perrone、Francesco Berardi

  DOI：10.1016/j.ejmech.2011.05.057

  日期：2011.9

  1-Cyclohexy1-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) and 2-Methoxy-5-methyl-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)butyl]benzamide 2 (RHM-1) represent leads for tumor diagnosis, given their high affinity at sigma(2) receptors. With the purpose of obtaining good candidates for sigma(2) PET tracers development, hybrid structures between 1 and 2 were designed. Excellent sigma(1)/sigma(2) selectivities were reached when 6,7-dimethoxytetrahydroisoquinoline was linked to an o-methoxy substituted arylamide (11a, 12a, 15a). and for these benzamides an intramolecular H-bond in the active conformation at the sigma sites, was hypothesized. However these excellent sigma(2) ligands were accompanied by interaction with P-gp. which may limit their use as sigma(2) receptor PET agents when tumors overexpress P-gp. Compound 15a whose P-gp interaction was just moderate represents an interesting tool for the development of sigma(2) PET tracers useful in tumors overexpressing P-gp. (C) 2011 Elsevier Masson SAS. All rights reserved.