2-hydroxy-6-methoxy-4-(2-methyloctan-2-yl)benzaldehyde | 1399049-47-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-hydroxy-6-methoxy-4-(2-methyloctan-2-yl)benzaldehyde
• CAS: 1399049-47-8
• 化学式: C₁₇H₂₆O₃
• 分子量: 278.392
• InChiKey: XWBDECMFAZBEFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.46
• 重原子数：
  20.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-hydroxy-6-methoxy-4-(2-methyloctan-2-yl)benzaldehyde 在 三溴化硼 、 potassium carbonate 、 1,3-二甲基咪唑二甲基膦 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 25.33h， 生成 3-Benzyl-5-hydroxy-7-(2-methyloctan-2-yl)chromen-2-one
  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
• 作为产物：
  描述：

  2,6-Dimethoxy-4-(2-methyloctan-2-yl)benzaldehyde 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 2-hydroxy-6-methoxy-4-(2-methyloctan-2-yl)benzaldehyde
  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

• 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。