N-acetyl-1-(4'-chlorophenyl)-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline | 861221-63-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: N-acetyl-1-(4'-chlorophenyl)-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 2-acetyl-1-(4'-chlorophenyl)-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline；1-[1-(4-chlorophenyl)-7-hydroxy-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethanone
• CAS: 861221-63-8
• 化学式: C₁₈H₁₈ClNO₃
• 分子量: 331.799
• InChiKey: REQGNOFNXWKWNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-acetyl-1-(4'-chlorophenyl)-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline 、 [11C]methyl iodide 在 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 0.05h， 生成 2-acetyl-1-(4'-chlorophenyl)-6-methoxy-7-(11C)methoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Closing in on the AMPA receptor: Synthesis and evaluation of 2-acetyl-1-(4′-chlorophenyl)-6-methoxy-7-[11C]methoxy-1,2,3,4-tetrahydroisoquinoline as a potential PET tracer

  摘要：

  2-Acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, one of the most potent non-competitive AMPA antagonists described to date, has been labelled with carbon-11 and tritium and evaluated as a potential ligand for in vivo imaging of AMPA receptors using PET. The carbon-11 labelled compound showed good initial brain uptake in rats, but with rapid clearance and relatively homogenous distribution. In saturation binding studies, the tritiated racemic ligand was found to be highly potent with a K(d) of 14.8 +/- 1.8 nM. We conclude that the low receptor density labelled with this compound, its rapid clearance from the CNS and low specific binding makes it unsuitable as an in vivo PET imaging agent for AMPA receptors. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.03.034
• 作为产物：
  描述：

  4-(2-氨基乙基)-2-甲氧基苯酚 在 potassium carbonate 、 三氟乙酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 7.0h， 生成 N-acetyl-1-(4'-chlorophenyl)-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Closing in on the AMPA receptor: Synthesis and evaluation of 2-acetyl-1-(4′-chlorophenyl)-6-methoxy-7-[11C]methoxy-1,2,3,4-tetrahydroisoquinoline as a potential PET tracer

  摘要：

  2-Acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, one of the most potent non-competitive AMPA antagonists described to date, has been labelled with carbon-11 and tritium and evaluated as a potential ligand for in vivo imaging of AMPA receptors using PET. The carbon-11 labelled compound showed good initial brain uptake in rats, but with rapid clearance and relatively homogenous distribution. In saturation binding studies, the tritiated racemic ligand was found to be highly potent with a K(d) of 14.8 +/- 1.8 nM. We conclude that the low receptor density labelled with this compound, its rapid clearance from the CNS and low specific binding makes it unsuitable as an in vivo PET imaging agent for AMPA receptors. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.03.034

文献信息

• Synthesis of carbon-11 and fluorine-18 labeled N-acetyl-1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as new potential PET AMPA receptor ligands
  作者：Mingzhang Gao、Deyuan Kong、Abraham Clearfield、Qi-Huang Zheng

  DOI：10.1016/j.bmcl.2006.01.042

  日期：2006.4

  New carbon-11 and fluorine-18 labeled N-acetyl-1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were designed and synthesized as potential positron emission tomography AMPA (2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid) receptor ligands to image brain diseases. The single crystal structure of the most potent compound N-acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-te

  设计并合成了新的碳11和氟18标记的N-乙酰基-1-芳基-6,7-二甲氧基-1,2,3,4-四氢异喹啉衍生物，作为潜在的正电子发射断层扫描仪AMPA（2-amino-3- （3-羟基-5-甲基异恶唑-4-基）丙酸）受体配体对大脑疾病进行成像。最先报道最有效的化合物N-乙酰基-1-（4'-氯苯基）-6,7-二甲氧基-1,2,3,4-四氢异喹啉（5a）的单晶结构。
• Closing in on the AMPA receptor: Synthesis and evaluation of 2-acetyl-1-(4′-chlorophenyl)-6-methoxy-7-[11C]methoxy-1,2,3,4-tetrahydroisoquinoline as a potential PET tracer
  作者：Erik Årstad、Rosaria Gitto、Alba Chimirri、Roberta Caruso、Andrew Constanti、David Turton、Sue P. Hume、Rabia Ahmad、Lyn S. Pilowsky、Sajinder K. Luthra

  DOI：10.1016/j.bmc.2006.03.034

  日期：2006.7.15

  2-Acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, one of the most potent non-competitive AMPA antagonists described to date, has been labelled with carbon-11 and tritium and evaluated as a potential ligand for in vivo imaging of AMPA receptors using PET. The carbon-11 labelled compound showed good initial brain uptake in rats, but with rapid clearance and relatively homogenous distribution. In saturation binding studies, the tritiated racemic ligand was found to be highly potent with a K(d) of 14.8 +/- 1.8 nM. We conclude that the low receptor density labelled with this compound, its rapid clearance from the CNS and low specific binding makes it unsuitable as an in vivo PET imaging agent for AMPA receptors. (c) 2006 Elsevier Ltd. All rights reserved.