3-benzyl-5-hydroxy-2H-chromen-2-one | 1439930-28-5

• 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: 3-benzyl-5-hydroxy-2H-chromen-2-one
• 英文别名: 3-benzyl-5-hydroxy-2H-1-benzopyran-2-one；3-Benzyl-5-hydroxychromen-2-one；3-benzyl-5-hydroxychromen-2-one
• CAS: 1439930-28-5
• 化学式: C₁₆H₁₂O₃
• 分子量: 252.269
• InChiKey: MVFFYIFEUZGLKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  3-benzyl-5-hydroxy-2H-chromen-2-one 、 氯磷酸二乙酯 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 168.25h， 以47%的产率得到3-benzyl-2-oxo-2H-1-benzopyran-5-yl diethyl phosphate
  参考文献：
  名称：

  Synthesis, biochemical evaluation, and molecular modeling of organophosphate-coumarin hybrids as potent and selective butyrylcholinesterase inhibitors

  摘要：

  A small library of new organophosphorylated warfarins and 3-benzylcoumarins were synthesized and evaluated for in vitro cholinesterase inhibition by Ellman's method. Most of the compounds were found to be selective for butyrylcholinesterase (BChE) over acetylcholinesterase (AChE), with IC50 values ranging from 0.363 mu M to 53.0 mu M determined after 15 s of enzyme exposure. Comparison of the most potent compound, 3b with its constitutional isomer 2b revealed the high importance of phosphate positioning. Reversed selectivity and a 100-fold reduction in anti-BChE activity was observed when the organophosphate was attached to the benzyl instead of the coumarin. Docking calculations suggest that 3b binds initially as a transition state mimic with nearoptimal phosphate orientation relative to S198 and occupation of the oxyanion hole prior to phosphorylation. These results might inspire the design of a new type of non-neuropathic and irreversible coumarin-based inhibitor against BChE.

  DOI：

  10.1016/j.bmcl.2020.127213
• 作为产物：
  描述：

  反式肉桂醛 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 26.5h， 生成 3-benzyl-5-hydroxy-2H-chromen-2-one
  参考文献：
  名称：

  Synthesis, biochemical evaluation, and molecular modeling of organophosphate-coumarin hybrids as potent and selective butyrylcholinesterase inhibitors

  摘要：

  A small library of new organophosphorylated warfarins and 3-benzylcoumarins were synthesized and evaluated for in vitro cholinesterase inhibition by Ellman's method. Most of the compounds were found to be selective for butyrylcholinesterase (BChE) over acetylcholinesterase (AChE), with IC50 values ranging from 0.363 mu M to 53.0 mu M determined after 15 s of enzyme exposure. Comparison of the most potent compound, 3b with its constitutional isomer 2b revealed the high importance of phosphate positioning. Reversed selectivity and a 100-fold reduction in anti-BChE activity was observed when the organophosphate was attached to the benzyl instead of the coumarin. Docking calculations suggest that 3b binds initially as a transition state mimic with nearoptimal phosphate orientation relative to S198 and occupation of the oxyanion hole prior to phosphorylation. These results might inspire the design of a new type of non-neuropathic and irreversible coumarin-based inhibitor against BChE.

  DOI：

  10.1016/j.bmcl.2020.127213

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.
• Synthesis, biochemical evaluation, and molecular modeling of organophosphate-coumarin hybrids as potent and selective butyrylcholinesterase inhibitors
  作者：Lee J. Macklin、Jason P. Schwans

  DOI：10.1016/j.bmcl.2020.127213

  日期：2020.7

  A small library of new organophosphorylated warfarins and 3-benzylcoumarins were synthesized and evaluated for in vitro cholinesterase inhibition by Ellman's method. Most of the compounds were found to be selective for butyrylcholinesterase (BChE) over acetylcholinesterase (AChE), with IC50 values ranging from 0.363 mu M to 53.0 mu M determined after 15 s of enzyme exposure. Comparison of the most potent compound, 3b with its constitutional isomer 2b revealed the high importance of phosphate positioning. Reversed selectivity and a 100-fold reduction in anti-BChE activity was observed when the organophosphate was attached to the benzyl instead of the coumarin. Docking calculations suggest that 3b binds initially as a transition state mimic with nearoptimal phosphate orientation relative to S198 and occupation of the oxyanion hole prior to phosphorylation. These results might inspire the design of a new type of non-neuropathic and irreversible coumarin-based inhibitor against BChE.