4'-methoxy-3-nitro-3',5-dipropyl-biphenyl-2-ol | 1315334-14-5

• 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'-methoxy-3-nitro-3',5-dipropyl-biphenyl-2-ol
• 英文别名: 4'-methoxy-3-nitro-3',5-dipropylbiphenyl-2-ol；2-(4-Methoxy-3-propylphenyl)-6-nitro-4-propylphenol
• CAS: 1315334-14-5
• 化学式: C₁₉H₂₃NO₄
• 分子量: 329.396
• InChiKey: PXARWHYVJSSOJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 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'-methoxy-3-nitro-3',5-dipropyl-biphenyl-2-ol 在 tin(II) chloride dihdyrate 作用下， 以 乙醇 、 水 为溶剂， 反应 72.08h， 生成 3-acetamido-4'-methoxy-3',5-dipropylbiphenyl-2-ol
  参考文献：
  名称：

  Synthesis of Tetrahydrohonokiol Derivates and Their Evaluation for Cytotoxic Activity against CCRF-CEM Leukemia, U251 Glioblastoma and HCT-116 Colon Cancer Cells

  摘要：

  二联苯新木脂素类化合物如和厚朴酚和木兰脂素是亚洲药用植物厚朴的主要活性成分,它们具有多种药理和生物活性。其中,对各种肿瘤细胞系的细胞毒性和肿瘤生长抑制活性已有充分研究记录。 为进一步阐明和厚朴酚衍生物的细胞毒性作用,以四氢和厚朴酚为骨架进行了衍生化研究。衍生化包括引入硝基和氨基等官能团以及烷基化。 通过这种方式,对18个衍生物(其中13个为此前未描述的化合物)在CCRF-CEM白血病细胞、U251胶质母细胞瘤和HCT-116结肠癌细胞中进行了评估。结果显示,在10 μM的测试浓度下,这些化合物在三种测试细胞系中均未显示出显著的细胞毒性作用。

  DOI：

  10.3390/molecules19011223
• 作为产物：
  描述：

  和厚朴酚 在 palladium on activated charcoal 、 氢气 、 硝酸 、 potassium hydroxide 作用下， 以 乙酸乙酯 为溶剂， 生成 4'-methoxy-3-nitro-3',5-dipropyl-biphenyl-2-ol
  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

• 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.
• Synthesis of Tetrahydrohonokiol Derivates and Their Evaluation for Cytotoxic Activity against CCRF-CEM Leukemia, U251 Glioblastoma and HCT-116 Colon Cancer Cells
  作者：Marketa Bernaskova、Nadine Kretschmer、Wolfgang Schuehly、Antje Huefner、Robert Weis、Rudolf Bauer

  DOI：10.3390/molecules19011223

  日期：——

  Biphenyl neolignans such as honokiol and magnolol, which are the major active constituents of the Asian medicinal plant Magnolia officinalis, are known to exert a multitude of pharmacological and biological activities. Among these, cytotoxic and tumor growth inhibitory activity against various tumour cell lines are well-documented. To further elucidate the cytotoxic effects of honokiol derivatives, derivatizations were performed using tetrahydrohonokiol as a scaffold. The derivatizations comprised the introduction of functional groups, e.g., nitro and amino groups, as well as alkylation. This way, 18 derivatives, of which 13 were previously undescribed compounds, were evaluated against CCRF-CEM leukemia cells, U251 glioblastoma and HCT-116 colon cancer cells. The results revealed no significant cytotoxic effects in any of the three tested cell lines at a test concentration of 10 µM.

  二联苯新木脂素类化合物如和厚朴酚和木兰脂素是亚洲药用植物厚朴的主要活性成分,它们具有多种药理和生物活性。其中,对各种肿瘤细胞系的细胞毒性和肿瘤生长抑制活性已有充分研究记录。 为进一步阐明和厚朴酚衍生物的细胞毒性作用,以四氢和厚朴酚为骨架进行了衍生化研究。衍生化包括引入硝基和氨基等官能团以及烷基化。 通过这种方式,对18个衍生物(其中13个为此前未描述的化合物)在CCRF-CEM白血病细胞、U251胶质母细胞瘤和HCT-116结肠癌细胞中进行了评估。结果显示,在10 μM的测试浓度下,这些化合物在三种测试细胞系中均未显示出显著的细胞毒性作用。
• 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.