(6-甲氧基萘-1-基)-(1-戊基吲哚-3-基)甲酮 | 824961-41-3

• 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
• 中文名称: (6-甲氧基萘-1-基)-(1-戊基吲哚-3-基)甲酮
• 英文名称: (6-methoxy-1-naphthalenyl)(1-pentyl-1H-indol-3-yl)methanone
• 英文别名: JWH-166；1-pentyl-3-(6-methoxy-1-naphthoyl)indole；Methanone, (6-methoxy-1-naphthalenyl)(1-pentyl-1H-indol-3-yl)-；(6-methoxynaphthalen-1-yl)-(1-pentylindol-3-yl)methanone
• CAS: 824961-41-3
• 化学式: C₂₅H₂₅NO₂
• 分子量: 371.479
• InChiKey: JCOOBICVPDFZNX-UHFFFAOYSA-N

物化性质

• 沸点：
  562.8±25.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：10mg/mL； DMSO：10mg/mL；乙醇：10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (6-甲氧基萘-1-基)三氟甲磺酸酯 在 palladium diacetate 甲酸 、 草酰氯 、 1,3-双(二苯基膦)丙烷 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 (6-甲氧基萘-1-基)-(1-戊基吲哚-3-基)甲酮
  参考文献：
  名称：

  Structure–activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists

  摘要：

  In an effort to improve indole-based CB2 cannabinoid receptor ligands and also to develop SAR for both the CB1 and CB2 receptors, 47 indole derivatives were prepared and their CB1 and CB2 receptor affinities were determined. The indole derivatives include 1-propyl- and 1-pentyl-3-(1-naphthoyl)indoles both with and without a 2-methyl substituent. Naphthoyl substituents include 4- and 7-alkyl groups as well as 2-, 4-, 6-, 7-methoxy and 4-ethoxy groups. The effects of these substituents on receptor affinities are discussed and structure-activity relationships are presented. In the course of this work three new highly selective CB2 receptor agonists were identified, 1-propyl-3-(4-methyl-1-naphthoylindole (JWH-120), 1-propyl-2-methyl-3-(6-methoxy-1-naphthoylindole (JWH-151), and 1-pentyl-3-(2-methoxy-1-naphthoylindole (JWH-267). GTPgammaS assays indicated that JWH-151 is a full agonist at CB2, while JWH-120 and JWH-267 are partial agonists. Molecular modeling and receptor docking studies were carried out on a set of 3-(4-propyl-1-naphthoyl)indoles, a set of 3-(6-methoxy-1-naphthoyl)indoles and the pair of N-pentyl-3-(2-methoxy-1-naphthoyl)indoles. Docking studies indicated that the CB1 receptor affinities of these compounds were consistent with their aromatic stacking interactions in the aromatic microdomain of the CB1 receptor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.09.050

文献信息

• CB2-selective cannabinoid analogues
  申请人：Martin R. Billy

  公开号：US20050009903A1

  公开（公告）日：2005-01-13

  Cannabinoid analogues that exhibit specificity for the CB 2 cannabinoid receptor are provided. The analogues are 1-methoxy-, 1-deoxy-11-hydroxy- and 11-hydroxy-1-methoxy-Δ 8 -tetrahydrocannabinols and 1-alkyl-3(1-naphthoyl)indoles. The compounds are useful for the treatment of pain (especially pain resulting from inflammation) and cancer (especially glioma tumors).

  提供了对CB2大麻素受体具有特异性的大麻素类似物。这些类似物是1-甲氧基-、1-去氧-11-羟基-和11-羟基-1-甲氧基-Δ8-四氢大麻酚以及1-烷基-3(1-萘酰)吲哚。这些化合物对于治疗疼痛（尤其是由炎症引起的疼痛）和癌症（尤其是胶质瘤）具有用途。
• Structure–activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists
  作者：John W. Huffman、Gulay Zengin、Ming-Jung Wu、Jianzhong Lu、George Hynd、Kristen Bushell、Alicia L.S. Thompson、Simon Bushell、Cindy Tartal、Dow P. Hurst、Patricia H. Reggio、Dana E. Selley、Michael P. Cassidy、Jenny L. Wiley、Billy R. Martin

  DOI：10.1016/j.bmc.2004.09.050

  日期：2005.1

  In an effort to improve indole-based CB2 cannabinoid receptor ligands and also to develop SAR for both the CB1 and CB2 receptors, 47 indole derivatives were prepared and their CB1 and CB2 receptor affinities were determined. The indole derivatives include 1-propyl- and 1-pentyl-3-(1-naphthoyl)indoles both with and without a 2-methyl substituent. Naphthoyl substituents include 4- and 7-alkyl groups as well as 2-, 4-, 6-, 7-methoxy and 4-ethoxy groups. The effects of these substituents on receptor affinities are discussed and structure-activity relationships are presented. In the course of this work three new highly selective CB2 receptor agonists were identified, 1-propyl-3-(4-methyl-1-naphthoylindole (JWH-120), 1-propyl-2-methyl-3-(6-methoxy-1-naphthoylindole (JWH-151), and 1-pentyl-3-(2-methoxy-1-naphthoylindole (JWH-267). GTPgammaS assays indicated that JWH-151 is a full agonist at CB2, while JWH-120 and JWH-267 are partial agonists. Molecular modeling and receptor docking studies were carried out on a set of 3-(4-propyl-1-naphthoyl)indoles, a set of 3-(6-methoxy-1-naphthoyl)indoles and the pair of N-pentyl-3-(2-methoxy-1-naphthoyl)indoles. Docking studies indicated that the CB1 receptor affinities of these compounds were consistent with their aromatic stacking interactions in the aromatic microdomain of the CB1 receptor. (C) 2004 Elsevier Ltd. All rights reserved.