AM2233 | 444912-55-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: AM2233
• 英文别名: 2-iodophenyl-(1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl)methanone；(2-iodophenyl)-[1-[[(2R)-1-methylpiperidin-2-yl]methyl]indol-3-yl]methanone
• CAS: 444912-55-4
• 化学式: C₂₂H₂₃IN₂O
• 分子量: 458.342
• InChiKey: KSLCYQTUSSEGPT-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  25.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  AM2233 在 四(三苯基膦)钯 、 六正丁基二锡 、 盐酸 、 sodium iodide 、 chloroamine-T 作用下， 以 甲苯 、 乙醇 为溶剂， 生成 [131I](R)-2-iodophenyl-[1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl]methanone
  参考文献：
  名称：

  Potent Cannabinergic Indole Analogues as Radioiodinatable Brain Imaging Agents for the CB1 Cannabinoid Receptor

  摘要：

  A series of novel aminoalkylindoles was synthesized in an effort to develop compounds that are potent agonists at the CB1 cannabinoid receptor and that are also easily labeled with radioisotopes of iodine for biochemical and imaging studies. 2-iodophenyl-[1-(l-methylpiperidin2-ylmethyl)]-1H-indol-3-yllmethanone (8, AM2233) had a very high affinity for the rat CB1 receptor, with most of the affinity residing with the (R)-enantiomer. Radioiodinated 8, (R)-8, and (S)-8 were prepared by radioiododestannylation of the tributyltin analogues in high yields, radiochemical purities, and specific radioactivities. In a mouse hippocampal membrane preparation with [I-131](R)-8 as radioligand, racemic 8 exhibited a K-i value of 0.2 nM compared with 1.6 nM for WIN55212-2. In autoradiographic experiments with mouse brain sections, the distribution of radioiodinated 8 was consistent with that of brain CB1 receptors. Again, very little specific binding was seen with the (S)-enantiomer [I-131](S)-8 and none occurred with the (R)-enantiomer [I-131] (R)-8 in sections from CB1 receptor knockout mice. Radioiodinated 8 thus appears to be a suitable radioligand for studies of CB1 cannabinoid receptors.

  DOI：

  10.1021/jm050135l
• 作为产物：
  描述：

  (R)-(+)-2-chloromethyl-1-methylpiperidine 在 三氯化铝 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 AM2233
  参考文献：
  名称：

  Potent Cannabinergic Indole Analogues as Radioiodinatable Brain Imaging Agents for the CB1 Cannabinoid Receptor

  摘要：

  A series of novel aminoalkylindoles was synthesized in an effort to develop compounds that are potent agonists at the CB1 cannabinoid receptor and that are also easily labeled with radioisotopes of iodine for biochemical and imaging studies. 2-iodophenyl-[1-(l-methylpiperidin2-ylmethyl)]-1H-indol-3-yllmethanone (8, AM2233) had a very high affinity for the rat CB1 receptor, with most of the affinity residing with the (R)-enantiomer. Radioiodinated 8, (R)-8, and (S)-8 were prepared by radioiododestannylation of the tributyltin analogues in high yields, radiochemical purities, and specific radioactivities. In a mouse hippocampal membrane preparation with [I-131](R)-8 as radioligand, racemic 8 exhibited a K-i value of 0.2 nM compared with 1.6 nM for WIN55212-2. In autoradiographic experiments with mouse brain sections, the distribution of radioiodinated 8 was consistent with that of brain CB1 receptors. Again, very little specific binding was seen with the (S)-enantiomer [I-131](S)-8 and none occurred with the (R)-enantiomer [I-131] (R)-8 in sections from CB1 receptor knockout mice. Radioiodinated 8 thus appears to be a suitable radioligand for studies of CB1 cannabinoid receptors.

  DOI：

  10.1021/jm050135l

文献信息

• Potent Cannabinergic Indole Analogues as Radioiodinatable Brain Imaging Agents for the CB1 Cannabinoid Receptor
  作者：Hongfeng Deng、Andrew N. Gifford、Alexander M. Zvonok、Guangjian Cui、Xiuyan Li、Pusheng Fan、Jeffrey R. Deschamps、Judith L. Flippen-Anderson、S. John Gatley、Alexandros Makriyannis

  DOI：10.1021/jm050135l

  日期：2005.10.1

  A series of novel aminoalkylindoles was synthesized in an effort to develop compounds that are potent agonists at the CB1 cannabinoid receptor and that are also easily labeled with radioisotopes of iodine for biochemical and imaging studies. 2-iodophenyl-[1-(l-methylpiperidin2-ylmethyl)]-1H-indol-3-yllmethanone (8, AM2233) had a very high affinity for the rat CB1 receptor, with most of the affinity residing with the (R)-enantiomer. Radioiodinated 8, (R)-8, and (S)-8 were prepared by radioiododestannylation of the tributyltin analogues in high yields, radiochemical purities, and specific radioactivities. In a mouse hippocampal membrane preparation with [I-131](R)-8 as radioligand, racemic 8 exhibited a K-i value of 0.2 nM compared with 1.6 nM for WIN55212-2. In autoradiographic experiments with mouse brain sections, the distribution of radioiodinated 8 was consistent with that of brain CB1 receptors. Again, very little specific binding was seen with the (S)-enantiomer [I-131](S)-8 and none occurred with the (R)-enantiomer [I-131] (R)-8 in sections from CB1 receptor knockout mice. Radioiodinated 8 thus appears to be a suitable radioligand for studies of CB1 cannabinoid receptors.