4'-methoxy-3',5-di-n-propyl-[1,1'-biphenyl]-2-ol | 82793-36-0

• 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',5-di-n-propyl-[1,1'-biphenyl]-2-ol
• 英文别名: 4'-methoxy-3',5-dipropyl-biphenyl-2-ol；4'-methoxy-3',5-dipropylbiphenyl-2-ol；4'-methoxy-5,3'-dipropylbiphenyl-2-ol；Magreth-1；2-(4-methoxy-3-propylphenyl)-4-propylphenol
• CAS: 82793-36-0
• 化学式: C₁₉H₂₄O₂
• 分子量: 284.398
• InChiKey: HFEJJSAHPYKAPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  21
• 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：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4'-methoxy-3',5-di-n-propyl-[1,1'-biphenyl]-2-ol 在 硝酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 0.17h， 以78%的产率得到4'-methoxy-3-nitro-3',5-dipropyl-biphenyl-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 、 potassium hydroxide 作用下， 生成 4'-methoxy-3',5-di-n-propyl-[1,1'-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

• Design and synthesis of 4-O-methylhonokiol analogs as inhibitors of cyclooxygenase-2 (COX-2) and PGF1 production
  作者：Bit Lee、Jae-Hwan Kwak、Shin-Won Huang、Jae-Yong Jang、Sanglae Lim、Young-Shin Kwak、Kiho Lee、Hyung Sook Kim、Sang-Bae Han、Jin-Tae Hong、Heesoon Lee、Sukgil Song、Seung-Yong Seo、Jae-Kyung Jung

  DOI：10.1016/j.bmc.2012.03.028

  日期：2012.5

  A series of novel 4-O-methylhonokiol analogs were synthesized in light of revealing structure-activity relationship for inhibitory effect of COX-2 enzyme. The key strategy of the molecular design was oriented towards modification of the potential metabolic soft spots (e. g., phenol and olefin) or by altering the polar surface area via incorporating heterocycles such as isoxazole and triazole. Most of all exhibited the inhibitory effects on COX-2 and PGF(1) production but not macrophage NO production. Especially, aryl carbamates 10 and 11 exhibited more potent inhibitory activity against COX-2 and PGF(1) production. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.
• 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.
• Design and synthesis of ten biphenyl-neolignan derivatives and their in vitro inhibitory potency against cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4-formation
  作者：Wolfgang Schühly、Antje Hüfner、Eva M. Pferschy-Wenzig、Elke Prettner、Michael Adams、Antje Bodensieck、Olaf Kunert、Asije Oluwemimo、Ernst Haslinger、Rudolf Bauer

  DOI：10.1016/j.bmc.2009.05.018

  日期：2009.7

  A set of ten derivatives of methylhonokiol, an anti-inflammatory active biphenyl-type neolignan from Magnolia grandiflora, has been evaluated for their in vitro cyclooxygenase-1/2 (COX-1/2) inhibitory activity using assays with purified prostaglandin H synthase (PGHS)-1 and PGHS-2 enzymes as well as for their 5-lipoxygenase (5-LOX) mediated LTB4 formation inhibitory activity using an assay with activated human polymorphonuclear leukocytes. The derivatization reactions included methylation, acetylation, hydrogenation, epoxydation and isomerization. Five of the derivatives are new to science. The most active compound against COX-1 and COX-2 was methylhonokiol with IC50 values of 0.1 mu M, whereas the most active compound against LTB4 formation was (E)-3'-propenyl-5-(2-propenyl)-biphenyl-2,4'-diol with an IC50 value of 1.0 mu M. Structure-activity relationship studies showed that the polarity of the derivatives plays a crucial role in their activity towards COX-1/2 enzyme and 5-LOX mediated LTB4 formation. (C) 2009 Elsevier Ltd. All rights reserved.
• 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。