6-hydroxy-5,7,8-trimethyl-3-(2-methylbenzyl)-2H-chromen-2-one | 1439930-37-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 6-hydroxy-5,7,8-trimethyl-3-(2-methylbenzyl)-2H-chromen-2-one
• 英文别名: 6-Hydroxy-5,7,8-trimethyl-3-[(2-methylphenyl)methyl]chromen-2-one；6-hydroxy-5,7,8-trimethyl-3-[(2-methylphenyl)methyl]chromen-2-one
• CAS: 1439930-37-6
• 化学式: C₂₀H₂₀O₃
• 分子量: 308.377
• InChiKey: YMIVMZWPBGUNRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,5-dihydroxy-3,4,6-trimethyl-benzaldehyde 、 α-甲基肉桂醛 在 potassium carbonate 、 1,3-二甲基咪唑二甲基膦 作用下， 以 甲苯 为溶剂， 反应 0.83h， 以73%的产率得到6-hydroxy-5,7,8-trimethyl-3-(2-methylbenzyl)-2H-chromen-2-one
  参考文献：
  名称：

  Antagonists for the Orphan G-Protein-Coupled Receptor GPR55 Based on a Coumarin Scaffold

  摘要：

  The orphan G-protein-coupled receptor GPR55, which is activated by 1-lysophosphatidylinositol and interacts with cannabinoid (CB) receptor ligands, has been proposed as a new potential drug target for the treatment of diabetes, Parkinson's disease, neuropathic pain, and cancer. We applied beta-arrestin assays to identify 3-substituted coumarins as a novel class of antagonists and performed an extensive structure-activity relationship study for GPR55. Selectivity versus the related receptors CB1, CB2, and GPR18 was assessed. Among the 7-unsubstituted coumarins selective, competitive GPR55 antagonists were identified, such as 3-(2-hydroxybenzyl)-5-isopropyl-8-methyl-2H-chromen-2-one (12, PSB-SB-489, IC50 = 1.77 mu M, pA(2) = 0.547 mu M). Derivatives with long alkyl chains in position 7 were potent, possibly allosteric GPR55 antagonists which showed ancillary CB receptor affinity. 7-(1,1-Dimethyloctyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (69, PSB-SB-487, IC50 = 0.113 mu M, K-B = 0.561 mu M) and 7-(1,1-dimethylheptyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (67, PSB-SB-1203, IC50 = 0.261 mu M) were the most potent GPR55 antagonists of the present series.

  DOI：

  10.1021/jm4005175

文献信息

• Antagonists for the Orphan G-Protein-Coupled Receptor GPR55 Based on a Coumarin Scaffold
  作者：Viktor Rempel、Nicole Volz、Franziska Gläser、Martin Nieger、Stefan Bräse、Christa E. Müller

  DOI：10.1021/jm4005175

  日期：2013.6.13

  The orphan G-protein-coupled receptor GPR55, which is activated by 1-lysophosphatidylinositol and interacts with cannabinoid (CB) receptor ligands, has been proposed as a new potential drug target for the treatment of diabetes, Parkinson's disease, neuropathic pain, and cancer. We applied beta-arrestin assays to identify 3-substituted coumarins as a novel class of antagonists and performed an extensive structure-activity relationship study for GPR55. Selectivity versus the related receptors CB1, CB2, and GPR18 was assessed. Among the 7-unsubstituted coumarins selective, competitive GPR55 antagonists were identified, such as 3-(2-hydroxybenzyl)-5-isopropyl-8-methyl-2H-chromen-2-one (12, PSB-SB-489, IC50 = 1.77 mu M, pA(2) = 0.547 mu M). Derivatives with long alkyl chains in position 7 were potent, possibly allosteric GPR55 antagonists which showed ancillary CB receptor affinity. 7-(1,1-Dimethyloctyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (69, PSB-SB-487, IC50 = 0.113 mu M, K-B = 0.561 mu M) and 7-(1,1-dimethylheptyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2-one (67, PSB-SB-1203, IC50 = 0.261 mu M) were the most potent GPR55 antagonists of the present series.