3′,5-diallyl-4′-ethoxy-[1,1′-biphenyl]-2-ol | 1315333-95-9

• 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: 3′,5-diallyl-4′-ethoxy-[1,1′-biphenyl]-2-ol
• 英文别名: 3',5-diallyl-4'-ethoxy-[1,1'-biphenyl]-2-ol；3',5-diallyl-4'-ethoxybiphenyl-2-ol；Magreth-16b；2-(4-ethoxy-3-prop-2-enylphenyl)-4-prop-2-enylphenol
• CAS: 1315333-95-9
• 化学式: C₂₀H₂₂O₂
• 分子量: 294.393
• InChiKey: IGROZJFLUONIRU-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：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  3′,5-diallyl-4′-ethoxy-[1,1′-biphenyl]-2-ol 在 硝酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 0.02h， 以50%的产率得到4'-O-ethyl-3-nitro-honokiol
  参考文献：
  名称：

  Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter

  摘要：

  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。

  DOI：

  10.3390/molecules23102536
• 作为产物：
  描述：

  硫酸二乙酯 、 和厚朴酚 在 potassium hydroxide 作用下， 生成 3′,5-diallyl-4′-ethoxy-[1,1′-biphenyl]-2-ol 、 2-O-ethylhonokiol
  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

• Synthesis and in vitro antitumor evaluation of honokiol derivatives
  作者：Meilin Zhu、Bohan Li、Hui Ma、Xuenan Huang、Haotian Wang、Yiqun Dai、Yu Li、Hong-Mei Li、Cheng-Zhu Wu

  DOI：10.1016/j.bmcl.2019.126849

  日期：2020.1

  is a natural bioactive neolignan and has been widely researched and structural modified as an anticancer agent. In this paper, 18 honokiol derivatives were synthesized and investigated for their antitumor activity. Among these, the promising compound 5a exhibited much higher anti-proliferative activity with IC50 value of 10.41 μM. Transwell assays showed that 5a could significantly inhibit the invasion

  厚朴酚是一种天然的生物活性新木脂素，已被广泛研究并被结构修饰为抗癌剂。本文合成了18种厚朴酚衍生物，并对其抗肿瘤活性进行了研究。其中，有希望的化合物5a表现出更高的抗增殖活性，IC50值为10.41μM。Transwell分析表明，5a可以显着抑制2.5μM的I-10细胞的侵袭和迁移，蛋白印迹实验进一步证实了HIF-1α及其相关下游蛋白MMP-2和MMP-的下调。 9。总体而言，这些结果为厚朴酚衍生物的进一步结构优化提供了有用的建议。
• Synthesis of Either C2- or C4′-Alkylated Derivatives of Honokiol and Their Biological Evaluation for Anti-inflammatory Activity
  作者：San-ha Lee、Xiang Fei、Chaelin Lee、Hien Thi Thu Do、Inmoo Rhee、Seung-Yong Seo

  DOI：10.1248/cpb.c19-00207

  日期：2019.9.1

  promising anti-inflammatory activity for the treatment of various diseases. There are many efforts on the synthesis and structure-activity relationship of honokiol derivatives. However, regioselective O-alkylation of honokiol remains a challenge and serves as a tool to provide not only some derivatives but also chemical probes for target identification and mode of action. In this study, we examined the reaction

  厚朴酚是从木兰中分离得到的双酚新木脂，据报道具有用于治疗各种疾病的有希望的抗炎活性。厚朴酚衍生物的合成及其构效关系方面有许多努力。然而，厚朴酚的区域选择性O-烷基化仍然是一个挑战，并不仅提供了一些衍生物，而且提供了化学探针来鉴定靶标和作用方式的工具。在这项研究中，我们检查了区域选择性O-烷基化的反应条件，其中合成了厚朴酚的C2和C4'-烷基化类似物，并评估了其对一氧化氮生成和环氧合酶2表达的抑制活性。此外，我们成功地基于C4'合成了由生物素和二苯甲酮组成的潜在光亲和探针
• Structural Modification of Honokiol, a Biphenyl Occurring in Magnolia officinalis: the Evaluation of Honokiol Analogues as Inhibitors of Angiogenesis and for Their Cytotoxicity and Structure–Activity Relationship
  作者：Liang Ma、Jinying Chen、Xuewei Wang、Xiaolin Liang、Youfu Luo、Wei Zhu、Tianen Wang、Ming Peng、Shucai Li、Shi Jie、Aihua Peng、Yuquan Wei、Lijuan Chen

  DOI：10.1021/jm200830u

  日期：2011.10.13

  Honokiol, widely known as an antitumor agent, has been used as an antiangiogenesis drug lead. In this paper, 47 honokiol analogues and derivatives were investigated for their antiangiogenic activity by application of the transgenic zebrafish screening model, antiproliferative and cytotoxic activity against HUVECs, and three tumor cell lines by MTT assay. 3',5-Diallyl-2, 4'-dihydroxy-[1,1'-biphen-yl]-3,5'-dicarbaldehyde (8c) was found to suppress the newly grown segmental vessels from the dorsal aorta of zebrafish and prevent inappropriate vascularization as well as exhibit more potent inhibitory effects on the proliferation of HUVECs, A549, HepG2, and LL/2 cells (IC50 = 15.1, 30.2, 10.7, and 21.7 mu M, respectively) than honokiol (IC50 = 52.6, 35.0, 16.5, and 65.4 mu M, respectively). Analogue 8c also effectively inhibited the migration and capillary-like tube formation of HUVECs in vitro. The antiangiogenic effect and antiproliferative activity of these structurally modified honokiol analogues and derivatives have led to the establishment of a structure-activity relationship.
• 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.
• 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。