N-[2-[[4-[(4-(125I)iodanylphenyl)methyl]piperidin-1-yl]methyl]-3H-benzimidazol-5-yl]methanesulfonamide | 1258291-01-8

• 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: N-[2-[[4-[(4-(125I)iodanylphenyl)methyl]piperidin-1-yl]methyl]-3H-benzimidazol-5-yl]methanesulfonamide
• CAS: 1258291-01-8
• 化学式: C₂₁H₂₅IN₄O₂S
• 分子量: 522.521
• InChiKey: ZJNLXQGQBWLKIU-ONBQKKEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  86.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-{2-[4-(4-iodobenzyl)-piperidin-1-ylmethyl]benzimidazol-5-yl}-methanesulfonamide 在 四(三苯基膦)钯 、 六甲基二锡 、 盐酸 、 sodium iodide 、 双氧水 作用下， 以 甲苯 、 乙醇 、 水 为溶剂， 反应 6.67h， 生成 N-[2-[[4-[(4-(125I)iodanylphenyl)methyl]piperidin-1-yl]methyl]-3H-benzimidazol-5-yl]methanesulfonamide
  参考文献：
  名称：

  Synthesis and biological evaluation of radio-iodinated benzimidazoles as SPECT imaging agents for NR2B subtype of NMDA receptor

  摘要：

  In this study, the benzimidazole derivatives were synthesized and evaluated as imaging agents for the NR2B subtype of NMDA receptor. Among these ligands, 2-{[4-(4-iodobenzyl)piperidin-1-yl]methyl}benzimidazol-5-ol (8) and N-{2-[4-(4-iodobenzyl)-piperidin-1-ylmethyl]benzoimidazol-5-yl}-methanesulfonamide (9) exhibited high affinity for the NR2B subunit (K-i values; 7.28 nM for 8 and 5.75 nM for 9). In vitro autoradiography experiments demonstrated high accumulation in the forebrain regions but low in the cerebellum for both [I-125]8 and [I-125]9. These regional distributions of the radioligands correlated with the expression of the NR2B subunit. The in vitro binding of these ligands was inhibited by NR2B antagonist but not by other site ligands, which suggested the high selectivity of [I-125]8 and [I-125]9 for the NR2B subunit. In mice, the regional brain uptakes of [I-125]8 and [I-125]9 at 5-180 min after administration were 0.42-0.56% and 0.44-0.67% dose/g, respectively. The brain-to-blood ratio of [I-125]8 at 180 min was reduced by 34% in the presence of non-radioactive ligands and by 59% in the presence of the NR2B ligand Ro-25,6981. These results indicated that [I-125]8 could be partially bound to the NR2B subunit in vivo. Although the brain uptake of these benzimidazole derivatives was too low to allow for in vivo SPECT imaging, these compounds might be useful scaffolds for the development of imaging probes specific for the NMDA receptors. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.053

文献信息

• Synthesis and biological evaluation of radio-iodinated benzimidazoles as SPECT imaging agents for NR2B subtype of NMDA receptor
  作者：Takeshi Fuchigami、Hiroshi Yamaguchi、Mikako Ogawa、Le Biao、Morio Nakayama、Mamoru Haratake、Yasuhiro Magata

  DOI：10.1016/j.bmc.2010.08.053

  日期：2010.11

  In this study, the benzimidazole derivatives were synthesized and evaluated as imaging agents for the NR2B subtype of NMDA receptor. Among these ligands, 2-[4-(4-iodobenzyl)piperidin-1-yl]methyl}benzimidazol-5-ol (8) and N-2-[4-(4-iodobenzyl)-piperidin-1-ylmethyl]benzoimidazol-5-yl}-methanesulfonamide (9) exhibited high affinity for the NR2B subunit (K-i values; 7.28 nM for 8 and 5.75 nM for 9). In vitro autoradiography experiments demonstrated high accumulation in the forebrain regions but low in the cerebellum for both [I-125]8 and [I-125]9. These regional distributions of the radioligands correlated with the expression of the NR2B subunit. The in vitro binding of these ligands was inhibited by NR2B antagonist but not by other site ligands, which suggested the high selectivity of [I-125]8 and [I-125]9 for the NR2B subunit. In mice, the regional brain uptakes of [I-125]8 and [I-125]9 at 5-180 min after administration were 0.42-0.56% and 0.44-0.67% dose/g, respectively. The brain-to-blood ratio of [I-125]8 at 180 min was reduced by 34% in the presence of non-radioactive ligands and by 59% in the presence of the NR2B ligand Ro-25,6981. These results indicated that [I-125]8 could be partially bound to the NR2B subunit in vivo. Although the brain uptake of these benzimidazole derivatives was too low to allow for in vivo SPECT imaging, these compounds might be useful scaffolds for the development of imaging probes specific for the NMDA receptors. (C) 2010 Elsevier Ltd. All rights reserved.