N-(7-aminoheptyl)-2-(2-(((4αS,7S,7αR,12βS)-4α,9-dihydroxy-3-methyl-2,3,4,4α,5,6,7,7α-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)-2-oxoethoxy)acetamide | 1443990-87-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: N-(7-aminoheptyl)-2-(2-(((4αS,7S,7αR,12βS)-4α,9-dihydroxy-3-methyl-2,3,4,4α,5,6,7,7α-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)-2-oxoethoxy)acetamide
• 英文别名: 2-[2-[[(4R,4aS,7S,7aR,12bS)-4a,9-dihydroxy-3-methyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethoxy]-N-(7-aminoheptyl)acetamide
• CAS: 1443990-87-1
• 化学式: C₂₈H₄₂N₄O₆
• 分子量: 530.665
• InChiKey: WLKHNSCCDAJTQP-DVAYJBEHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methylcarbamoylmethoxyacetic acid 、 N-(7-aminoheptyl)-2-(2-(((4αS,7S,7αR,12βS)-4α,9-dihydroxy-3-methyl-2,3,4,4α,5,6,7,7α-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)-2-oxoethoxy)acetamide 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-((4aS,7S,7aR,12bS)-4a,9-dihydroxy-3-methyl-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)-2-((3,7,17-trioxo-5-oxa-2,8,16-triazaoctadecan-18-yl)oxy)acetamide
  参考文献：
  名称：

  [EN] THERAPEUTIC COMPOUNDS
  [FR] COMPOSÉS THÉRAPEUTIQUES

  摘要：

  其中的盐也被披露。还披露了包括I式化合物的药物组合物，用于制备I式化合物的过程，用于制备I式化合物的有用中间体以及使用I式化合物的治疗方法。

  公开号：

  WO2016138142A1
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 生成 N-(7-aminoheptyl)-2-(2-(((4αS,7S,7αR,12βS)-4α,9-dihydroxy-3-methyl-2,3,4,4α,5,6,7,7α-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)-2-oxoethoxy)acetamide
  参考文献：
  名称：

  Bivalent Ligands That Target μ Opioid (MOP) and Cannabinoid1 (CB₁) Receptors Are Potent Analgesics Devoid of Tolerance

  摘要：

  Given that mu opioid (MOP) and canabinoid (CB1) receptors are colocalized in various regions of the central nervous system and have been reported to associate as heteromer (MOP-CB1) in cultured cells, the possibility of functional, endogenous MOP CB1 in nociception and other pharmacologic effects has been raised. As a first step in investigating this possibility, we have synthesized a series of bivalent ligands 1-5 that contain both mu agonist and CB1 antagonist pharmacophores for use as tools to study the functional interaction between MOP and CB1 receptors in vivo. Immunofluorescent studies on HEK293 cells coexpressing both receptors suggested 5 (20-atom spacer) to be the only member of the series that bridges the protomers of the heteromer. Antinociceptive testing in mice revealed 5 to be the most potent member of the series. As neither a mixture of monovalent ligands 9 + 10 nor bivalents 2-5 produced tolerance in mice, MOR-CB1 apparently is not an important target for reducing tolerance.

  DOI：

  10.1021/jm4005219

文献信息

• [EN] ANALGESIC CONJUGATES<br/>[FR] CONJUGUÉS ANALGÉSIQUES
  申请人：UNIV MINNESOTA

  公开号：WO2014124317A1

  公开（公告）日：2014-08-14

  The invention provides analgesic conjugates having a mu opioid receptor agonist linked to a mGluR5 antagonist, and to methods for producing analgesia using such compounds.

  该发明提供了一种镇痛共轭物，其中包含与mGluR5拮抗剂连接的mu阿片受体激动剂，并提供了使用这种化合物产生镇痛作用的方法。
• Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR₅)
  作者：Eyup Akgün、Muhammad I. Javed、Mary M. Lunzer、Michael D. Powers、Yuk Y. Sham、Yoshikazu Watanabe、Philip S. Portoghese

  DOI：10.1021/acs.jmedchem.5b01245

  日期：2015.11.12

  Chemokine release promotes cross-talk between opioid and chemokine receptors that in part leads to reduced efficacy of morphine in the treatment of chronic pain. On the basis of the possibility that a MOR-CCR5 heteromer is involved in such cross-talk, we have synthesized bivalent ligands (MCC series) that contain mu opioid agonist and CCR5 antagonist pharmacophores linked through homologous spacers (14-24 atoms). When tested on lipopolysaccharide-inflamed mice, a member of the series (MCC22; 3e) with a 22-atom spacer exhibited profound antinociception (i.t. ED50 = 0.0146 pmol/mouse) that was 2000X greater than morphine. Moreover, MCC22 was similar to 3500X more potent than a mixture of mu agonist and CCR5 antagonist monovalent ligands. These data strongly suggest that MCC22 acts by bridging the protomers of a MOR-CCR5 heteromer having a TM5,6 interface. Molecular simulation studies are consistent with such bridging. This study supports the MOR-CCR5 heteromer as a novel target for the treatment of chronic pain.