2-[4-(4-fluorobenzyl)piperidin-1-yl]methyl-5-aminobenzimidazol | 1310689-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-[4-(4-fluorobenzyl)piperidin-1-yl]methyl-5-aminobenzimidazol
• 英文别名: 2-[[4-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]-3H-benzimidazol-5-amine
• CAS: 1310689-11-2
• 化学式: C₂₀H₂₃FN₄
• 分子量: 338.428
• InChiKey: ILCIACIRAZJBFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  57.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-(4-fluorobenzyl)piperidin-1-yl]methyl-5-aminobenzimidazol 在 盐酸 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 N-(2-([4-(4-fluorobenzyl)piperidin-1-yl]methyl)benzimidazol-5-yl)methanesulfonamide dihydrochloride
  参考文献：
  名称：

  Synthesis, evaluation and metabolic studies of radiotracers containing a 4-(4-[18F]-fluorobenzyl)piperidin-1-yl moiety for the PET imaging of NR2B NMDA receptors

  摘要：

  In this study, novel specific PET radioligands containing the 4-(4-fluorobenzyl)piperidine moiety and selectively antagonistic for the NR2B subunit containing NMDA receptors were developed. Two antagonists, RGH-896 (1a) and 4-(4-fluorobenzyl)piperidinyl-1-methyl-2-benzimidazol-5-ol (2a), belonging to two different structural families, were radiolabeled by an aromatic nucleophilic radiofluorination followed by a reduction of the para-position carbonyl function. Radiotracers [F-18]1a, [F-18]2a or the pattern 4-(4-[(18)[F]-fluorobenzyl)piperidine ([(18)[F]6) demonstrated an identical in vivo behavior with high accumulation of radioactivity in bone and cartilage which would suggest a radiodefluorination of the radiotracers. The identification of metabolites from 6 by LC-MS-MS confirmed the significant degree of defluorination as a result of the in vivo hydroxylation in the benzyl ring. In conclusion, [(18)[F]1a or [(18)[F]2a are not suitable for imaging the NR2B NMDA receptors due to their poor brain penetration. We also argue for a cautious use of the radiolabeled pattern, 4-(4-[(18)[F]-fluorobenzyl)piperidine, to develop PET radiotracers.(C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.03.013
• 作为产物：
  描述：

  4-(4’-氟苄基)哌啶 在 palladium on carbon 、 氢气 、 sodium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0~70.0 ℃ 、150.0 kPa 条件下， 反应 18.5h， 生成 2-[4-(4-fluorobenzyl)piperidin-1-yl]methyl-5-aminobenzimidazol
  参考文献：
  名称：

  Synthesis, evaluation and metabolic studies of radiotracers containing a 4-(4-[18F]-fluorobenzyl)piperidin-1-yl moiety for the PET imaging of NR2B NMDA receptors

  摘要：

  In this study, novel specific PET radioligands containing the 4-(4-fluorobenzyl)piperidine moiety and selectively antagonistic for the NR2B subunit containing NMDA receptors were developed. Two antagonists, RGH-896 (1a) and 4-(4-fluorobenzyl)piperidinyl-1-methyl-2-benzimidazol-5-ol (2a), belonging to two different structural families, were radiolabeled by an aromatic nucleophilic radiofluorination followed by a reduction of the para-position carbonyl function. Radiotracers [F-18]1a, [F-18]2a or the pattern 4-(4-[(18)[F]-fluorobenzyl)piperidine ([(18)[F]6) demonstrated an identical in vivo behavior with high accumulation of radioactivity in bone and cartilage which would suggest a radiodefluorination of the radiotracers. The identification of metabolites from 6 by LC-MS-MS confirmed the significant degree of defluorination as a result of the in vivo hydroxylation in the benzyl ring. In conclusion, [(18)[F]1a or [(18)[F]2a are not suitable for imaging the NR2B NMDA receptors due to their poor brain penetration. We also argue for a cautious use of the radiolabeled pattern, 4-(4-[(18)[F]-fluorobenzyl)piperidine, to develop PET radiotracers.(C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.03.013

文献信息

• Synthesis, evaluation and metabolic studies of radiotracers containing a 4-(4-[18F]-fluorobenzyl)piperidin-1-yl moiety for the PET imaging of NR2B NMDA receptors
  作者：Romain Labas、Gwénaëlle Gilbert、Olivier Nicole、Martine Dhilly、Ahmed Abbas、Olivier Tirel、Alain Buisson、Joël Henry、Louisa Barré、Danièle Debruyne、Franck Sobrio

  DOI：10.1016/j.ejmech.2011.03.013

  日期：2011.6

  In this study, novel specific PET radioligands containing the 4-(4-fluorobenzyl)piperidine moiety and selectively antagonistic for the NR2B subunit containing NMDA receptors were developed. Two antagonists, RGH-896 (1a) and 4-(4-fluorobenzyl)piperidinyl-1-methyl-2-benzimidazol-5-ol (2a), belonging to two different structural families, were radiolabeled by an aromatic nucleophilic radiofluorination followed by a reduction of the para-position carbonyl function. Radiotracers [F-18]1a, [F-18]2a or the pattern 4-(4-[(18)[F]-fluorobenzyl)piperidine ([(18)[F]6) demonstrated an identical in vivo behavior with high accumulation of radioactivity in bone and cartilage which would suggest a radiodefluorination of the radiotracers. The identification of metabolites from 6 by LC-MS-MS confirmed the significant degree of defluorination as a result of the in vivo hydroxylation in the benzyl ring. In conclusion, [(18)[F]1a or [(18)[F]2a are not suitable for imaging the NR2B NMDA receptors due to their poor brain penetration. We also argue for a cautious use of the radiolabeled pattern, 4-(4-[(18)[F]-fluorobenzyl)piperidine, to develop PET radiotracers.(C) 2011 Elsevier Masson SAS. All rights reserved.