(4-甲基萘-1-基)-[1-(2-吗啉-4-基乙基)吲哚-3-基]甲酮 | 133438-58-1

• 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: (4-甲基萘-1-基)-[1-(2-吗啉-4-基乙基)吲哚-3-基]甲酮
• 中文别名: 甲酮,(4-甲基-1-萘基)[1-[2-(4-吗啉基)乙基]-1H-吲哚-3-基]-
• 英文名称: (4-methyl-1-naphthalenyl)[1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl]methanone
• 英文别名: 3-(4-methylnaphthalene-1-carbonyl)-1-[2-(morpholin-4-yl)ethyl]-1H-indole；1-[2-(4-morpholino)ethyl]-3-(4-methyl-1-naphthoyl)indole；JWH-193；(1-(2-Morpholin-4-ylethyl)indol-3-yl)-4-methylnaphthalen-1-ylmethanone；(4-methylnaphthalen-1-yl)-[1-(2-morpholin-4-ylethyl)indol-3-yl]methanone
• CAS: 133438-58-1
• 化学式: C₂₆H₂₆N₂O₂
• 分子量: 398.505
• InChiKey: ICKWPPYMDARCKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-甲基萘-1-基)-[1-(2-吗啉-4-基乙基)吲哚-3-基]甲酮 在 lithium aluminium tetrahydride 、 三氯化铝 作用下， 以 乙醚 为溶剂， 反应 48.0h， 以41%的产率得到(1-(2-morpholin-4-ylethyl)indol-3-yl)-4-methylnaphthalen-1-ylmethane
  参考文献：
  名称：

  3-Indolyl-1-naphthylmethanes: new cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB1 cannabinoid receptor

  摘要：

  A series of 1-pentyl-1H-indol-3-yl-(1-naphthyl)methanes (9 11) and 2-methyl-1-pentyl-1H-indol-3-yl-(1-naphthyl)methanes (12-14) have been synthesized to investigate the hypothesis that cannabimimetic 3-(1-naphthoyl)indoles interact with the CB I receptor by hydrogen bonding to the carbonyl group. Indoles 9-11 have significant (K-i 17-23 nM) receptor affinity, somewhat less than that of the corresponding naphthoylindoles (5, 15, 16). 2-Methyl-1-indoles 12-14 have little affinity for the CB1 receptor, in contrast to 2-methyl-3-(1-naphthoyl)indoles 17-19, which have affinities comparable to those of 5, 15, 16. A cannabimimetic indene hydrocarbon (26) was synthesized and found to have K-i = 26 +/- 4 nM. Molecular modeling and receptor docking studies of naphthoylindole 16, its 2-methyl congener (19) and indolyl-1-naphthylmethanes 11 and 14, combined with the receptor affinities of these cannabimimetic indoles, strongly suggest that these cannabinoid receptor ligands bind primarily by aromatic stacking interactions in the transmembrane helix 3-4-5-6 region of the CB1 receptor. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00451-0
• 作为产物：
  描述：

  4-甲基-1-萘甲酸 在 氯化亚砜 、 二氯乙基铝 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 (4-甲基萘-1-基)-[1-(2-吗啉-4-基乙基)吲哚-3-基]甲酮
  参考文献：
  名称：

  Aminoalkylindoles: Structure-Activity Relationships of Novel Cannabinoid Mimetics

  摘要：

  Aminoalkylindoles (AAIs) are a novel series of cannabinoid receptor ligands. In this report we disclose the structural features of AAIs which are important for binding to this receptor as measured by inhibition of binding of [H-3]Win 55212-2 (5). Functional activity in the mouse vas deferens is also noted and used to distinguish agonists from potential antagonists. The key structural features for potent cannabinoid activity in this series are a bicyclic (naphthyl) substituent at the 3-position, a small (II) substituent at the 2-position, and an aminoethyl (morpholinoethyl) substituent at the 1-position. A 6-bromo analog, Win 54461 (31), has been identified as a potential cannabinoid receptor antagonist. Modeling experiments were done to develop a pharmacophore and also to compare AAI structures with those of classical cannabinoids. The fact that the cannabinoid AAIs arose out of work on a series of cyclooxygenase inhibitors makes sense now that an endogenous cannabinoid ligand has been identified which is a derivative of arachidonic acid. Because of their unique structures and physical properties, AAIs provide useful tools to study the structure and function of the cannabinoid receptor(s).

  DOI：

  10.1021/jm00016a013

文献信息

• PERIPHERALLY-ACTING CANNABINOID RECEPTOR AGONISTS FOR CHRONIC PAIN
  申请人：The Regents of the University of California

  公开号：US20150239859A1

  公开（公告）日：2015-08-27

  Peripherally acting cannabinoid agonist compounds, pharmaceutical compositions, and methods of using them are presented.

  本文介绍了外周作用的大麻素激动剂化合物、制药组合物以及使用它们的方法。
• TEST KIT FOR THE QUANTITATIVE DETERMINATION OF NARCOTIC DRUGS
  申请人：CHIRON AS

  公开号：US20150204893A1

  公开（公告）日：2015-07-23

  A test kit for the quantitative determination of narcotic drugs comprising (A) series of sealed vessels, each vessel containing a deuterium free isotopologue of a narcotic drug in exactly defined concentrations and quantities, wherein the isotopologue differs from vessel to vessel and—wherein the quantities of the isotopologue differ from vessel to vessel or are the same for all vessels; and/or (B) series of sealed vessels, each vessel containing in exactly defined concentrations and quantities the same isotopologue in quantities which differ from vessel to vessel; wherein the free isotopologues are selected from narcotic drugs; prodrugs, salts, solvates, hydrates and polymorphs and contain at least three stable isotopes selected from the group consisting of 13 C, 15 N and 18 O in the molecule with a degree of labeling of at least 95 mol-%; the use of the test kit and a method for quantitatively determining narcotic drugs.

  一种用于定量测定麻醉药物的检测试剂盒，包括（A）一系列密封容器，每个容器中含有一种去氘同位素麻醉药物，其浓度和数量均被精确定义，其中同位素从容器到容器不同，同位素的数量在容器到容器之间不同或对所有容器都相同；和/或（B）一系列密封容器，每个容器中含有相同的同位素，其浓度和数量被精确定义，数量在容器到容器之间不同；其中自由同位素选自麻醉药物、前药、盐、溶剂、水合物和多晶形，并且在分子中至少包含三种稳定同位素，所述稳定同位素选自13C、15N和18O，其标记度至少为95摩尔％；使用该检测试剂盒和一种定量测定麻醉药物的方法。
• COMPOSITION AND METHODS TO IMPROVE STABILITY, DOSING, PHARMACODYNAMICS AND PRODUCT SHELF LIFE OF ENDOCANNABINOIDS, PHYTOCANNABINOIDS AND SYNTHETIC CANNABINOIDS DELIVERED BY NASAL INHALER
  申请人：Willinsky, Michael

  公开号：EP3247402A1

  公开（公告）日：2017-11-29
• US9347961B2
  申请人：——

  公开号：US9347961B2

  公开（公告）日：2016-05-24
• US9656981B2
  申请人：——

  公开号：US9656981B2

  公开（公告）日：2017-05-23