9-{4-[(2-chlorobenzyl)oxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 9-{4-[(2-chlorobenzyl)oxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione
• 英文别名: 9-[4-[(2-chlorophenyl)methoxy]phenyl]-3,3,6,6-tetramethyl-4,5,7,9-tetrahydro-2H-xanthene-1,8-dione
• 化学式: C₃₀H₃₁ClO₄
• 分子量: 491.027
• InChiKey: RUUQNJFWVPMAFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对羟基苯甲醛 在 硫酸 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 15.0h， 生成 9-{4-[(2-chlorobenzyl)oxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione
  参考文献：
  名称：

  Discovery, Synthesis, and Molecular Pharmacology of Selective Positive Allosteric Modulators of the δ-Opioid Receptor

  摘要：

  Allosteric modulators of G protein-coupled receptors (GPCRs) have a number of potential advantages compared to agonists or antagonists that bind to the orthosteric site of the receptor. These include the potential for receptor selectivity, maintenance of the temporal and spatial fidelity of signaling in vivo, the ceiling effect of the allosteric cooperativity which may prevent overdose issues, and engendering bias by differentially modulating distinct signaling pathways. Here we describe the discovery, synthesis, and molecular pharmacology of delta-opioid receptor-selective positive allosteric modulators (delta PAMs). These delta PAMs increase the affinity and/or efficacy of the orthosteric agonists leu-enkephalin, SNC80 and TAN67, as measured by receptor binding, G protein activation, beta-arrestin recruitment, adenylyl cyclase inhibition, and extracellular signal-regulated kinases (ERK) activation. As such, these compounds are useful pharmacological tools to probe the molecular pharmacology of the delta receptor and to explore the therapeutic potential of delta PAMs in diseases such as chronic pain and depression.

  DOI：

  10.1021/acs.jmedchem.5b00007

文献信息

• Discovery, Synthesis, and Molecular Pharmacology of Selective Positive Allosteric Modulators of the δ-Opioid Receptor
  作者：Neil T. Burford、Kathryn E. Livingston、Meritxell Canals、Molly R. Ryan、Lauren M. L. Budenholzer、Ying Han、Yi Shang、John J. Herbst、Jonathan O’Connell、Martyn Banks、Litao Zhang、Marta Filizola、Daniel L. Bassoni、Tom S. Wehrman、Arthur Christopoulos、John R. Traynor、Samuel W. Gerritz、Andrew Alt

  DOI：10.1021/acs.jmedchem.5b00007

  日期：2015.5.28

  Allosteric modulators of G protein-coupled receptors (GPCRs) have a number of potential advantages compared to agonists or antagonists that bind to the orthosteric site of the receptor. These include the potential for receptor selectivity, maintenance of the temporal and spatial fidelity of signaling in vivo, the ceiling effect of the allosteric cooperativity which may prevent overdose issues, and engendering bias by differentially modulating distinct signaling pathways. Here we describe the discovery, synthesis, and molecular pharmacology of delta-opioid receptor-selective positive allosteric modulators (delta PAMs). These delta PAMs increase the affinity and/or efficacy of the orthosteric agonists leu-enkephalin, SNC80 and TAN67, as measured by receptor binding, G protein activation, beta-arrestin recruitment, adenylyl cyclase inhibition, and extracellular signal-regulated kinases (ERK) activation. As such, these compounds are useful pharmacological tools to probe the molecular pharmacology of the delta receptor and to explore the therapeutic potential of delta PAMs in diseases such as chronic pain and depression.