Magreth-11b | 1315334-13-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Magreth-11b
• 英文别名: 2-[3-(2-bromopropyl)-4-methoxyphenyl]-4-prop-2-enylphenol
• CAS: 1315334-13-4
• 化学式: C₁₉H₂₁BrO₂
• 分子量: 361.279
• InChiKey: RUVFYCSQNLFKOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4'-甲氧基-3',5-二-2-丙烯基-(1,1'-联苯)-2-醇 在 三溴化硼 、 水 作用下， 以 二氯甲烷 为溶剂， 生成 Magreth-11a 、 Magreth-11b
  参考文献：
  名称：

  Modulation of GABA_A-Receptors by Honokiol and Derivatives: Subtype Selectivity and Structure–Activity Relationship

  摘要：

  A series of 31 analogues of the neolignan honokiol (a major constituent of Magnolia officinalis) was synthesized, and their effects on GABA(A) receptors expressed in Xenopus oocytes were investigated. Honokiol enhanced chloride currents (I-GABA) through GABA(A) receptors of seven different subunit compositions with EC50 values ranging from 23.4 mu M (alpha(5)beta(2)) to 59.6 mu M (alpha(1)beta(3)). Honolciol was most efficient on alpha(3)beta(2) (maximal IGABA enhancement 2386%) > alpha(2)beta(2) (1130%) > alpha(1)beta(2) (1034%) > alpha(1)beta(1) (260%)). On alpha(1)beta(2)-receptors, N-substituted compounds were most active with 3-acetylamino-4'-O-methylhonolciol (31), enhancing I-GABA by 2601% (EC50 (alpha(1)beta(2)) = 3.8 mu M). Pharmacophore modeling gave a model with an overall classification accuracy of 91% showing three hydrophobic regions, one acceptor and one donor region. Unlike honokiol, 31 was most efficient on alpha(2)beta(2)- (5204%) > alpha(3)beta(2)- (3671%) > alpha(1)beta(2)-receptors (2601%), suggesting a role of the acetamido group in subunit-dependent receptor modulation.

  DOI：

  10.1021/jm200186n

文献信息

• Mechanisms of Osteoclastogenesis Inhibition by a Novel Class of Biphenyl-Type Cannabinoid CB2 Receptor Inverse Agonists
  作者：Wolfgang Schuehly、Juan Manuel Viveros Paredes、Jonas Kleyer、Antje Huefner、Sharon Anavi-Goffer、Stefan Raduner、Karl-Heinz Altmann、Jürg Gertsch

  DOI：10.1016/j.chembiol.2011.05.012

  日期：2011.8

  The cannabinoid CB2 receptor is known to modulate osteoclast function by poorly understood mechanisms. Here, we report that the natural biphenyl neolignan 4'-O-methylhonokiol (MH) is a CB2 receptor-selective antiosteoclastogenic lead structure (K-i < 50 nM). Intriguingly, MH triggers a simultaneous G(i) inverse agonist response and a strong CB2 receptor-dependent increase in intracellular calcium. The most active inverse agonists from a library of MH derivatives inhibited osteoclastogenesis in RANK ligand-stimulated RAW264.7 cells and primary human macrophages. Moreover, these ligands potently inhibited the osteoclastogenic action of endocannabinoids. Our data show that CB2 receptor-mediated cAMP formation, but not intracellular calcium, is crucially involved in the regulation of osteoclastogenesis, primarily by inhibiting macrophage chemotaxis and TNF-alpha expression. MH is an easily accessible CB2 receptor-selective scaffold that exhibits a novel type of functional heterogeneity.
• Modulation of GABA_A-Receptors by Honokiol and Derivatives: Subtype Selectivity and Structure–Activity Relationship
  作者：Barbara Taferner、Wolfgang Schuehly、Antje Huefner、Igor Baburin、Katharina Wiesner、Gerhard F. Ecker、Steffen Hering

  DOI：10.1021/jm200186n

  日期：2011.8.11

  A series of 31 analogues of the neolignan honokiol (a major constituent of Magnolia officinalis) was synthesized, and their effects on GABA(A) receptors expressed in Xenopus oocytes were investigated. Honokiol enhanced chloride currents (I-GABA) through GABA(A) receptors of seven different subunit compositions with EC50 values ranging from 23.4 mu M (alpha(5)beta(2)) to 59.6 mu M (alpha(1)beta(3)). Honolciol was most efficient on alpha(3)beta(2) (maximal IGABA enhancement 2386%) > alpha(2)beta(2) (1130%) > alpha(1)beta(2) (1034%) > alpha(1)beta(1) (260%)). On alpha(1)beta(2)-receptors, N-substituted compounds were most active with 3-acetylamino-4'-O-methylhonolciol (31), enhancing I-GABA by 2601% (EC50 (alpha(1)beta(2)) = 3.8 mu M). Pharmacophore modeling gave a model with an overall classification accuracy of 91% showing three hydrophobic regions, one acceptor and one donor region. Unlike honokiol, 31 was most efficient on alpha(2)beta(2)- (5204%) > alpha(3)beta(2)- (3671%) > alpha(1)beta(2)-receptors (2601%), suggesting a role of the acetamido group in subunit-dependent receptor modulation.