3,3,6,6-tetramethyl-9-(4-((2-methylbenzyl)oxy)phenyl)-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: 3,3,6,6-tetramethyl-9-(4-((2-methylbenzyl)oxy)phenyl)-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione
• 英文别名: BMS-986187；3,3,6,6-tetramethyl-9-[4-[(2-methylphenyl)methoxy]phenyl]-4,5,7,9-tetrahydro-2H-xanthene-1,8-dione
• 化学式: C₃₁H₃₄O₄
• mdl: MFCD01873698
• 分子量: 470.609
• InChiKey: UEKIYVKPQNKSDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 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 3,3,6,6-tetramethyl-9-(4-((2-methylbenzyl)oxy)phenyl)-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

• [EN] POSITIVE ALLOSTERIC MODULATORS OF THE DELTA-OPIOID RECEPTOR<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR OPIOÏDE DELTA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016100605A1

  公开（公告）日：2016-06-23

  Described are the discovery, synthesis and pharmacological characterization of δ-opioid receptor-selective positive allosteric modulators (δ PAMs). These δ PAMs may increase the affinity and/or efficacy of the orthosteric agonists leu-enkephalin and SNC80, as measured by β-arrestin recruitment and adenylyl cyclase inhibition. The compounds may be useful pharmacological tools to probe the molecular pharmacology of the δ receptor and to explore the therapeutic potential of δ PAMs in diseases such as chronic pain and depression.

  本文描述了δ-阿片受体选择性正变构调节剂（δ PAMs）的发现、合成和药理学特征。这些δ PAMs可以通过β-阻滞素招募和腺苷酸环化酶抑制来增加正位激动剂亮-恩啡啶和SNC80的亲和力和/或功效。这些化合物可能是有用的药理学工具，用于探索δ受体的分子药理学和探索δ PAMs在慢性疼痛和抑郁等疾病的治疗潜力。
• POSITIVE ALLOSTERIC MODULATORS OF THE DELTA-OPIOID RECEPTOR
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20170370929A1

  公开（公告）日：2017-12-28

  Described are the discovery, synthesis and pharmacological characterization of δ-opioid receptor-selective positive allosteric modulators (δ PAMs). These δ PAMs may increase the affinity and/or efficacy of the orthosteric agonists leu-enkephalin and SNC80, as measured by β-arrestin recruitment and adenylyl cyclase inhibition. The compounds may be useful pharmacological tools to probe the molecular pharmacology of the δ receptor and to explore the therapeutic potential of δ PAMs in diseases such as chronic pain and depression.
• 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.