4-(1-butylcyclohexyl)-2-hydroxy-6-methoxybenzaldehyde | 1399049-50-3

• 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-(1-butylcyclohexyl)-2-hydroxy-6-methoxybenzaldehyde
• 英文别名: 4-(1-Butylcyclohexyl)-2-hydroxy-6-methoxybenzaldehyde
• CAS: 1399049-50-3
• 化学式: C₁₈H₂₆O₃
• 分子量: 290.403
• InChiKey: BQEBQCLTZBZZJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(1-butylcyclohexyl)-2-hydroxy-6-methoxybenzaldehyde 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， -78.0~180.0 ℃ 、700.01 kPa 条件下， 反应 1.08h， 生成 7-(1-butylcyclohexyl)-5-hydroxy-3-methyl-2H-chromen-2-one
  参考文献：
  名称：

  香豆素衍生物作为有效大麻素受体激动剂的合成和 SAR 评估

  摘要：

  我们报告了一系列作为大麻素受体配体的修饰香豆素的开发和广泛的构效关系评估。在放射性配体和 [ 35 S] GTPγS 结合测定中，确定了新配体的 CB 受体结合亲和力和功效。此外，我们使用基于配体的对接方法来验证经验观察结果。总之，确定了几个关键的结构要求。最有效的香豆素，如 3-丁基-7-(1-丁基环戊基)-5-羟基-2H-chromen-2-one ( 36b , K i CB 2 13.7 nM, EC 50 18 nM), 7-(1-丁基环己基)-5-羟基-3-丙基-2H-chromen-2-one ( 39b , K iCB 2 6.5 nM，EC 50 4.51 nM)显示具有低纳摩尔亲和力的CB 2选择性激动特性。

  DOI：

  10.1016/j.ejmech.2021.113354
• 作为产物：
  描述：

  4-(1-Butylcyclohexyl)-2,6-dimethoxybenzaldehyde 在 aluminum (III) chloride 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 4-(1-butylcyclohexyl)-2-hydroxy-6-methoxybenzaldehyde
  参考文献：
  名称：

  7-Alkyl-3-benzylcoumarins: A Versatile Scaffold for the Development of Potent and Selective Cannabinoid Receptor Agonists and Antagonists

  摘要：

  A series of 7-alkyl-3-benzylcoumarins was designed, synthesized, and tested at cannabinoid CB1 and CB2 receptors in radioligand binding and cAMP accumulation studies. 7-Alkyl-3-benzylcoumarins were found to constitute a versatile scaffold for obtaining potent CB receptor ligands with high potency at either CB1 or CB2 and a broad spectrum of efficacies. Fine-tuning of compound properties was achieved by small modifications of the substitution pattern. The most potent compounds of the present series include 5-methoxy-3-(2-methylbenzyl)-7-pentyl-2H-chromen-2-one (19a, PSB-SB-1201), a selective CB1 antagonist (K-i CB1 0.022 mu M), 5-methoxy-3-(2-methoxybenzyl)-7-pentyl-2H-chromen-2-one (21a, PSB-SB-1202), a dual CB1/CB2 agonist (CB1 K-i 0.032 mu M, EC50 0.056 mu M; CB2 K-i 0.049 mu M, EC50 0.014 mu M), 5-hydroxy-3-(2-hydroxybenzyl)-7-(2-methyloct-2-yl)-2H-chromen-2-one (25b, PSB-SB-1203), a dual CB1/CB2 ligand that blocks CB1 but activates CB2 receptors (CB1 K-i 0.244 mu M; CB2 K-i 0.210 mu M, EC50 0.054 mu M), and 7-(1-butylcyclopentyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (27b, PSB-SB-1204), a selective CB2 receptor agonist (CB1 K-i 1.59 mu M; CB2 K-i 0.068 mu M, EC50 0.048 mu M).

  DOI：

  10.1021/jm3008213

文献信息

• Effects of a Novel GPR55 Antagonist on the Arachidonic Acid Cascade in LPS-Activated Primary Microglial Cells
  作者：Soraya Wilke Saliba、Franziska Gläser、Anke Deckers、Albrecht Keil、Thomas Hurrle、Matthias Apweiler、Florian Ferver、Nicole Volz、Dominique Endres、Stefan Bräse、Bernd L. Fiebich

  DOI：10.3390/ijms22052503

  日期：——

  Neuroinflammation is a crucial process to maintain homeostasis in the central nervous system (CNS). However, chronic neuroinflammation is detrimental, and it is described in the pathogenesis of CNS disorders, including Alzheimer’s disease (AD) and depression. This process is characterized by the activation of immune cells, mainly microglia. The role of the orphan G-protein-coupled receptor 55 (GPR55) in inflammation has been reported in different models. However, its role in neuroinflammation in respect to the arachidonic acid (AA) cascade in activated microglia is still lacking of comprehension. Therefore, we synthesized a novel GPR55 antagonist (KIT 10, 0.1–25 µM) and tested its effects on the AA cascade in lipopolysaccharide (LPS, 10 ng / mL)-treated primary rat microglia using Western blot and EIAs. We show here that KIT 10 potently prevented the release of prostaglandin E2 (PGE2), reduced microsomal PGE2 synthase (mPGES-1) and cyclooxygenase-2 (COX-2) synthesis, and inhibited the phosphorylation of Ikappa B-alpha (IκB-α), a crucial upstream step of the inflammation-related nuclear factor-kappaB (NF-κB) signaling pathway. However, no effects were observed on COX-1 and -2 activities and mitogen-activated kinases (MAPK). In summary, the novel GPR55 receptor antagonist KIT 10 reduces neuroinflammatory parameters in microglia by inhibiting the COX-2/PGE2 pathway. Further experiments are necessary to better elucidate its effects and mechanisms. Nevertheless, the modulation of inflammation by GPR55 might be a new therapeutic option to treat CNS disorders with a neuroinflammatory background such as AD or depression.

  神经炎症是维持中枢神经系统(CNS)稳态的关键过程。然而，慢性神经炎症是有害的，并在CNS疾病的病理发生中描述，包括阿尔茨海默病(AD)和抑郁症。这个过程的特点是免疫细胞，主要是微胶质细胞的活化。孤儿G蛋白偶联受体55(GPR55)在炎症中的作用已经在不同的模型中报道过。然而，它在激活的微胶质细胞中相对于花生四烯酸(AA)级联的神经炎症中的作用仍缺乏理解。因此，我们合成了一种新的GPR55拮抗剂(KIT 10，0.1-25 µM)，并测试了其对脂多糖(LPS，10 ng/mL)处理的原代大鼠微胶质细胞中AA级联的影响，使用Western blot和EIAs。我们在这里展示，KIT 10有效地防止了前列腺素E2(PGE2)的释放，减少了微粒体PGE2合成酶(mPGES-1)和环氧合酶-2(COX-2)的合成，并抑制了Ikappa B-alpha(IκB-α)的磷酸化，这是与炎症相关的核因子-kappaB(NF-κB)信号通路的关键上游步骤。然而，对COX-1和-2活性以及有丝分裂原激活激酶(MAPK)没有影响。总之，新的GPR55受体拮抗剂KIT 10通过抑制COX-2/PGE2途径减少微胶质细胞中的神经炎症参数。进一步的实验需要更好地阐明其作用和机制。然而，通过GPR55调节炎症可能是治疗具有神经炎症背景的CNS疾病，如AD或抑郁症的新疗法选择。
• Synthesis and SAR evaluation of coumarin derivatives as potent cannabinoid receptor agonists
  作者：Florian Mohr、Thomas Hurrle、Lindsey Burggraaff、Lukas Langer、Martijn P. Bemelmans、Maximilian Knab、Martin Nieger、Gerard J.P. van Westen、Laura H. Heitman、Stefan Bräse

  DOI：10.1016/j.ejmech.2021.113354

  日期：2021.8

  We report the development and extensive structure-activity relationship evaluation of a series of modified coumarins as cannabinoid receptor ligands. In radioligand, and [35S]GTPγS binding assays the CB receptor binding affinities and efficacies of the new ligands were determined. Furthermore, we used a ligand-based docking approach to validate the empirical observed results. In conclusion, several

  我们报告了一系列作为大麻素受体配体的修饰香豆素的开发和广泛的构效关系评估。在放射性配体和 [ 35 S] GTPγS 结合测定中，确定了新配体的 CB 受体结合亲和力和功效。此外，我们使用基于配体的对接方法来验证经验观察结果。总之，确定了几个关键的结构要求。最有效的香豆素，如 3-丁基-7-(1-丁基环戊基)-5-羟基-2H-chromen-2-one ( 36b , K i CB 2 13.7 nM, EC 50 18 nM), 7-(1-丁基环己基)-5-羟基-3-丙基-2H-chromen-2-one ( 39b , K iCB 2 6.5 nM，EC 50 4.51 nM)显示具有低纳摩尔亲和力的CB 2选择性激动特性。
• 7-Alkyl-3-benzylcoumarins: A Versatile Scaffold for the Development of Potent and Selective Cannabinoid Receptor Agonists and Antagonists
  作者：Viktor Rempel、Nicole Volz、Sonja Hinz、Tadeusz Karcz、Irene Meliciani、Martin Nieger、Wolfgang Wenzel、Stefan Bräse、Christa E. Müller

  DOI：10.1021/jm3008213

  日期：2012.9.27

  A series of 7-alkyl-3-benzylcoumarins was designed, synthesized, and tested at cannabinoid CB1 and CB2 receptors in radioligand binding and cAMP accumulation studies. 7-Alkyl-3-benzylcoumarins were found to constitute a versatile scaffold for obtaining potent CB receptor ligands with high potency at either CB1 or CB2 and a broad spectrum of efficacies. Fine-tuning of compound properties was achieved by small modifications of the substitution pattern. The most potent compounds of the present series include 5-methoxy-3-(2-methylbenzyl)-7-pentyl-2H-chromen-2-one (19a, PSB-SB-1201), a selective CB1 antagonist (K-i CB1 0.022 mu M), 5-methoxy-3-(2-methoxybenzyl)-7-pentyl-2H-chromen-2-one (21a, PSB-SB-1202), a dual CB1/CB2 agonist (CB1 K-i 0.032 mu M, EC50 0.056 mu M; CB2 K-i 0.049 mu M, EC50 0.014 mu M), 5-hydroxy-3-(2-hydroxybenzyl)-7-(2-methyloct-2-yl)-2H-chromen-2-one (25b, PSB-SB-1203), a dual CB1/CB2 ligand that blocks CB1 but activates CB2 receptors (CB1 K-i 0.244 mu M; CB2 K-i 0.210 mu M, EC50 0.054 mu M), and 7-(1-butylcyclopentyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (27b, PSB-SB-1204), a selective CB2 receptor agonist (CB1 K-i 1.59 mu M; CB2 K-i 0.068 mu M, EC50 0.048 mu M).