4'-O-methyl-3-nitro-honokiol | 1315334-03-2

• 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: 4'-O-methyl-3-nitro-honokiol
• 英文别名: 2-(4-Methoxy-3-prop-2-enylphenyl)-6-nitro-4-prop-2-enylphenol
• CAS: 1315334-03-2
• 化学式: C₁₉H₁₉NO₄
• 分子量: 325.364
• InChiKey: JVQDQHUSQDBSFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4'-O-methyl-3-nitro-honokiol 在 tin(II) chloride dihdyrate 作用下， 以 乙醇 、 水 为溶剂， 生成 3-(N-acetylamino)-4'-O-methylhonokiol
  参考文献：
  名称：

  Nitrogenated honokiol derivatives allosterically modulate GABAA receptors and act as strong partial agonists

  摘要：

  In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignan honokiol together with its isomer magnolol are the main constituents of Magnolia bark extracts. We have previously identified a nitrogen-containing honokiol derivative (3-acetylamino-4'-O-methylhonokiol, AMH) as a high efficient modulator of GABA(A) receptors. Here we further elucidate the structure-activity relation of a series of nitrogenated biphenyl-neolignan derivatives by analysing allosteric modulation and agonistic effects on alpha(1)beta(2)gamma(2S) GABA(A) receptors. The strongest I-GABA enhancement was induced by compound 5 (3-acetamido-4'-ethoxy-3',5-dipropylbiphenyl-2-ol, E-max: 123.4 +/- 9.4% of IGABA-max) and 6 (5'-amino-2-ethoxy-3',5-dipropylbiphenyl-4'-ol, E-max: 117.7 +/- 13.5% of IGABA-max). Compound 5 displayed, however, a significantly higher potency (EC50 = 1.8 +/- 1.1 mu M) than compound 6 (EC50 = 20.4 +/- 4.3 mu M). Honokiol, AMH and four of the derivatives induced significant inward currents in the absence of GABA. Strong partial agonists were honokiol (inducing 78 +/- 6% of IGABA-max), AMH (63 +/- 6%), 5'-amino-2-O-methylhonokiol (1) (59 +/- 1%) and 2-methoxy-5'-nitro-3',5-dipropylbiphenyl-4'-ol (3) (52 +/- 1%). 3-N-Acetylamino-4'-ethoxy-3',5-dipropyl-biphenyl-4'-ol (5) and 3-amino-4'-ethoxy-3',5-dipropyl-biphenyl-4'-ol (7) were less efficacious but even more potent (5: EC50 = 6.9 +/- 1.0 mu M; 7: EC50 = 33.2 +/- 5.1 mu M) than the full agonist GABA. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.034
• 作为产物：
  描述：

  和厚朴酚 在 硝酸 、 potassium hydroxide 作用下， 以 乙酸乙酯 为溶剂， 生成 4'-O-methyl-3-nitro-honokiol
  参考文献：
  名称：

  Nitrogenated honokiol derivatives allosterically modulate GABAA receptors and act as strong partial agonists

  摘要：

  In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignan honokiol together with its isomer magnolol are the main constituents of Magnolia bark extracts. We have previously identified a nitrogen-containing honokiol derivative (3-acetylamino-4'-O-methylhonokiol, AMH) as a high efficient modulator of GABA(A) receptors. Here we further elucidate the structure-activity relation of a series of nitrogenated biphenyl-neolignan derivatives by analysing allosteric modulation and agonistic effects on alpha(1)beta(2)gamma(2S) GABA(A) receptors. The strongest I-GABA enhancement was induced by compound 5 (3-acetamido-4'-ethoxy-3',5-dipropylbiphenyl-2-ol, E-max: 123.4 +/- 9.4% of IGABA-max) and 6 (5'-amino-2-ethoxy-3',5-dipropylbiphenyl-4'-ol, E-max: 117.7 +/- 13.5% of IGABA-max). Compound 5 displayed, however, a significantly higher potency (EC50 = 1.8 +/- 1.1 mu M) than compound 6 (EC50 = 20.4 +/- 4.3 mu M). Honokiol, AMH and four of the derivatives induced significant inward currents in the absence of GABA. Strong partial agonists were honokiol (inducing 78 +/- 6% of IGABA-max), AMH (63 +/- 6%), 5'-amino-2-O-methylhonokiol (1) (59 +/- 1%) and 2-methoxy-5'-nitro-3',5-dipropylbiphenyl-4'-ol (3) (52 +/- 1%). 3-N-Acetylamino-4'-ethoxy-3',5-dipropyl-biphenyl-4'-ol (5) and 3-amino-4'-ethoxy-3',5-dipropyl-biphenyl-4'-ol (7) were less efficacious but even more potent (5: EC50 = 6.9 +/- 1.0 mu M; 7: EC50 = 33.2 +/- 5.1 mu M) than the full agonist GABA. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.034

文献信息

• Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter
  作者：Kristen Stout、Marketa Bernaskova、Gary Miller、Antje Hufner、Wolfgang Schuehly

  DOI：10.3390/molecules23102536

  日期：——

  In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignans honokiol and magnolol are the main constituents of Magnolia bark extracts. In the central nervous system, Magnolia bark preparations that contain honokiol are thought to primarily interact with γ-aminobutyric acid A (GABAA) receptors. However, stress responses inherently involve the noradrenergic system, which has not been investigated in the pharmacological mechanism of honokiol. We present here interactions of honokiol and other synthesized biphenyl-type neolignans and diphenylmethane analogs with the norepinephrine transporter (NET), which is responsible for the synaptic clearance of norepinephrine and the target of many anxiolytics. Of the synthesized compounds, 16 are new chemical entities, which are fully characterized. The 52 compounds tested show mild, non-potent interactions with NET (IC50 > 100 µM). It is thus likely that the observed anxiolytic effects of, e.g., Magnolia preparations, are not due to direct interaction with the noradrenergic system.

  在传统的亚洲药物系统中，玉兰属植物的根和茎皮制剂被广泛用于治疗焦虑和其他神经紊乱。双苯型新木兰醇和木兰醇是玉兰树皮提取物的主要成分。在中枢神经系统中，含有新木兰醇的玉兰树皮制剂被认为主要与γ-氨基丁酸A（GABAA）受体相互作用。然而，应激反应本质上涉及未在新木兰醇的药理机制中进行研究的去甲肾上腺素系统。我们在这里介绍了新木兰醇和其他合成的双苯型新木兰醇和二苯甲烷类似物与去甲肾上腺素转运蛋白（NET）的相互作用，该蛋白负责去甲肾上腺素的突触清除，是许多抗焦虑药物的靶点。在合成的化合物中，有16种是新的化学实体，已经完全表征。测试的52种化合物与NET显示出轻微、非强效的相互作用（IC50 > 100 µM）。因此，例如玉兰制剂的观察到的抗焦虑效果可能不是由于与去甲肾上腺素系统的直接相互作用。
• 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.
• Nitrogenated honokiol derivatives allosterically modulate GABAA receptors and act as strong partial agonists
  作者：Marketa Bernaskova、Angela Schoeffmann、Wolfgang Schuehly、Antje Hufner、Igor Baburin、Steffen Hering

  DOI：10.1016/j.bmc.2015.08.034

  日期：2015.10

  In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignan honokiol together with its isomer magnolol are the main constituents of Magnolia bark extracts. We have previously identified a nitrogen-containing honokiol derivative (3-acetylamino-4'-O-methylhonokiol, AMH) as a high efficient modulator of GABA(A) receptors. Here we further elucidate the structure-activity relation of a series of nitrogenated biphenyl-neolignan derivatives by analysing allosteric modulation and agonistic effects on alpha(1)beta(2)gamma(2S) GABA(A) receptors. The strongest I-GABA enhancement was induced by compound 5 (3-acetamido-4'-ethoxy-3',5-dipropylbiphenyl-2-ol, E-max: 123.4 +/- 9.4% of IGABA-max) and 6 (5'-amino-2-ethoxy-3',5-dipropylbiphenyl-4'-ol, E-max: 117.7 +/- 13.5% of IGABA-max). Compound 5 displayed, however, a significantly higher potency (EC50 = 1.8 +/- 1.1 mu M) than compound 6 (EC50 = 20.4 +/- 4.3 mu M). Honokiol, AMH and four of the derivatives induced significant inward currents in the absence of GABA. Strong partial agonists were honokiol (inducing 78 +/- 6% of IGABA-max), AMH (63 +/- 6%), 5'-amino-2-O-methylhonokiol (1) (59 +/- 1%) and 2-methoxy-5'-nitro-3',5-dipropylbiphenyl-4'-ol (3) (52 +/- 1%). 3-N-Acetylamino-4'-ethoxy-3',5-dipropyl-biphenyl-4'-ol (5) and 3-amino-4'-ethoxy-3',5-dipropyl-biphenyl-4'-ol (7) were less efficacious but even more potent (5: EC50 = 6.9 +/- 1.0 mu M; 7: EC50 = 33.2 +/- 5.1 mu M) than the full agonist GABA. (c) 2015 Elsevier Ltd. All rights reserved.