[1-(1-Methyl-piperidin-2-ylmethyl)-1H-indol-3-yl]-(4-nitro-naphthalen-1-yl)-methanone | 335160-60-6

• 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: [1-(1-Methyl-piperidin-2-ylmethyl)-1H-indol-3-yl]-(4-nitro-naphthalen-1-yl)-methanone
• 英文别名: [1-[(1-methylpiperidin-2-yl)methyl]indol-3-yl]-(4-nitronaphthalen-1-yl)methanone
• CAS: 335160-60-6
• 化学式: C₂₆H₂₅N₃O₃
• 分子量: 427.503
• InChiKey: HKTOILNOPHRIQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [1-(1-Methyl-piperidin-2-ylmethyl)-1H-indol-3-yl]-(4-nitro-naphthalen-1-yl)-methanone 在 盐酸 、 镍 、 肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 (4-Iodo-naphthalen-1-yl)-[1-(1-methyl-piperidin-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：

  4-硝基-1-萘甲酸 在 三氯化铝 、 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 [1-(1-Methyl-piperidin-2-ylmethyl)-1H-indol-3-yl]-(4-nitro-naphthalen-1-yl)-methanone
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of a Novel Series of Aminoalkylindoles with Potential for Imaging the Neuronal Cannabinoid Receptor by Positron Emission Tomography

  摘要：

  A new series of CB1 ligands with high binding affinity (K-i = 0.7-100 nM) and moderate lipophilicity (cLogD(7.4)) in the range of 2.1-4.5 has been synthesized. A structure-activity relationship study demonstrated that for the studied set of aminoalkylindoles, the molecular dipole of the ground state conformation within the series was inversely related to the affinity. The racemic ligand with highest affinity (0.7 nM), 3-(4-fluoronaphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole, was radiolabeled with F-18. This radioligand specifically labeled CB, receptors in mouse brain and accumulated in regions of high versus low CB1 receptor density in a ratio of 1.6. The displaceable radioactivity of one enantiomer in the brains of mice determined in a pretreatment study using the CB, antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) was nearly double that of the racemate for the same determination; therefore, the active enantiomer is a candidate for PET studies in animals. A pretreatement study for the other enantiomer found no displaceable radioactivity in the same group of mice; this result suggested the enantiomer was inactive.

  DOI：

  10.1021/jm0502743

文献信息

• Microwave-accelerated fluorodenitrations and nitrodehalogenations: expeditious routes to labeled PET ligands and fluoropharmaceuticals
  作者：Paul LaBeaume、Michael Placzek、Mathew Daniels、Ian Kendrick、Patrick Ng、Melissa McNeel、Roushan Afroze、Abigail Alexander、Rhiannon Thomas、Amy E. Kallmerten、Graham B. Jones

  DOI：10.1016/j.tetlet.2010.02.042

  日期：2010.4

  Methods for the expeditious fluorination of arenes have been investigated, using readily available fluoride sources. An optimized procedure for microwave-accelerated fluorodenitration has been developed, giving good to excellent yields in less than 10 min, rendering it practical for use in the preparation of F-18 labeled ligands for PET imaging. Application of the method in the synthesis of CNS agents is demonstrated, and a practical method for the preparation of Substrates is also presented. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and Structure−Activity Relationship of a Novel Series of Aminoalkylindoles with Potential for Imaging the Neuronal Cannabinoid Receptor by Positron Emission Tomography
  作者：Peter G. Willis、Olga A. Pavlova、Svetlana I. Chefer、D. Bruce Vaupel、Alexey G. Mukhin、Andrew G. Horti

  DOI：10.1021/jm0502743

  日期：2005.9.1

  A new series of CB1 ligands with high binding affinity (K-i = 0.7-100 nM) and moderate lipophilicity (cLogD(7.4)) in the range of 2.1-4.5 has been synthesized. A structure-activity relationship study demonstrated that for the studied set of aminoalkylindoles, the molecular dipole of the ground state conformation within the series was inversely related to the affinity. The racemic ligand with highest affinity (0.7 nM), 3-(4-fluoronaphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole, was radiolabeled with F-18. This radioligand specifically labeled CB, receptors in mouse brain and accumulated in regions of high versus low CB1 receptor density in a ratio of 1.6. The displaceable radioactivity of one enantiomer in the brains of mice determined in a pretreatment study using the CB, antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) was nearly double that of the racemate for the same determination; therefore, the active enantiomer is a candidate for PET studies in animals. A pretreatement study for the other enantiomer found no displaceable radioactivity in the same group of mice; this result suggested the enantiomer was inactive.
• 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.