(2E)-6-Methoxy-2-[(2-methylphenyl)methylidene]-1,2,3,4-tetrahydronaphthalen-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (2E)-6-Methoxy-2-[(2-methylphenyl)methylidene]-1,2,3,4-tetrahydronaphthalen-1-one
• 英文别名: (2E)-6-methoxy-2-[(2-methylphenyl)methylidene]-3,4-dihydronaphthalen-1-one
• 化学式: C₁₉H₁₈O₂
• 分子量: 278.351
• InChiKey: WHQIWBZNJPZJEZ-LFIBNONCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2E)-6-Methoxy-2-[(2-methylphenyl)methylidene]-1,2,3,4-tetrahydronaphthalen-1-one 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、206.84 kPa 条件下， 反应 1.0h， 生成 6-Methoxy-2-(2-methyl-benzyl)-3,4-dihydro-2H-naphthalen-1-one
  参考文献：
  名称：

  2-取代的3,4-二氢-2H-萘-1-酮（四氢萘酮）衍生物的合成及CYP24抑制活性。

  摘要：

  新型2-苄基和2-亚苄基-3,4-二氢-2H-萘-1-酮（四氢萘酮）衍生物的合成及其对肾脏线粒体25-羟基维生素D（3）24-羟化酶（CYP24）的抑制活性描述。与酮康唑相比，发现2-苄基四氢萘酮衍生物是非常弱的抑制剂（IC（50）20> 100 microM），而2-苄基四氢萘酮衍生物显示出有希望的抑制活性（活性最高的衍生物IC（50）0.9 microM）。 IC（50）20 microM）。

  DOI：

  10.1016/j.bmcl.2004.08.040
• 作为产物：
  描述：

  2-甲基苯甲醛 、 6-甲氧基-1-萘满酮 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 生成 (2E)-6-Methoxy-2-[(2-methylphenyl)methylidene]-1,2,3,4-tetrahydronaphthalen-1-one
  参考文献：
  名称：

  2-取代的3,4-二氢-2H-萘-1-酮（四氢萘酮）衍生物的合成及CYP24抑制活性。

  摘要：

  新型2-苄基和2-亚苄基-3,4-二氢-2H-萘-1-酮（四氢萘酮）衍生物的合成及其对肾脏线粒体25-羟基维生素D（3）24-羟化酶（CYP24）的抑制活性描述。与酮康唑相比，发现2-苄基四氢萘酮衍生物是非常弱的抑制剂（IC（50）20> 100 microM），而2-苄基四氢萘酮衍生物显示出有希望的抑制活性（活性最高的衍生物IC（50）0.9 microM）。 IC（50）20 microM）。

  DOI：

  10.1016/j.bmcl.2004.08.040

文献信息

• Synthesis and CYP24A1 inhibitory activity of (E)-2-(2-substituted benzylidene)- and 2-(2-substituted benzyl)-6-methoxy-tetralones
  作者：Ahmed S. Aboraia、Bart Makowski、Alba Bahja、David Prosser、Andrea Brancale、Glenville Jones、Claire Simons

  DOI：10.1016/j.ejmech.2010.07.001

  日期：2010.10

  A series of (E)-2-(2-substituted benzylidene)- and 2-(2-substituted benzyl)-6-methoxy-tetralones were prepared, using an efficient synthetic scheme, and evaluated for their inhibitory activity against cytochrome P450C24A1 (CYP24A1) hydroxylase. In general the reduced benzyl tetralones were more active than the parent benzylidene tetralones. The 2-ethyl and 2-trifluoromethyl benzyl tetralone derivatives (4c and 4b) showed optimal activity in this series with IC(50) values of 1 92 mu M and 2.08 mu M, respectively compared with the standard ketoconazole IC(50) 0.52 mu M. The 2-bromobenzyl tetralone (4d) showed a preference for CYP27A1 (IC(50) 59 nM) over CYP24A1 (IC(50) 163 mu M) and may be a useful lead in CYP27A1 inhibition studies The 2-ethylphenyl benzyl derivative (9c), which showed weak activity against the wild type CYP24A1 (IC(50) 25.57 mu M), exhibited enhanced inhibitory activity towards L148F and M416T mutants, this difference in activity for the L148F mutant has been explained using molecular modelling (C) 2010 Elsevier Masson SAS. All rights reserved.
• Novel Tetralone-Derived Retinoic Acid Metabolism Blocking Agents:  Synthesis and in Vitro Evaluation with Liver Microsomal and MCF-7 CYP26A1 Cell Assays
  作者：Sook Wah Yee、Laetitia Jarno、Mohamed Sayed Gomaa、Carole Elford、Li-Ling Ooi、Michael P. Coogan、Richard McClelland、Robert Ian Nicholson、Bronwen A. J. Evans、Andrea Brancale、Claire Simons

  DOI：10.1021/jm0501681

  日期：2005.11.1

  The potent inhibitory activity of novel 2-benzyltetralone and 2-benzylidenetetralone derivatives vs liver microsomal retinoic acid metabolizing enzymes and a MCF-7 CYP26A1 cell assay is described. In the liver microsomal assay, the 2-biphenylmethyl-6-hydroxytetralone derivatives 16a and 16b were found to be potent inhibitors (IC50 = 0.5 and 0.8 mu M) compared with the broad spectrum P450 inhibitor ketoconazole and the retinoid mimetic R115866 (IC50 = 18.0 and 9.0 mu M, respectively). In the MCF-7 CYP26A1 cell assay, the 2-(4-hydroxybenzyl)-6-methoxytetralone 5 and unsaturated benzylidene precursor 6 were found to be the most potent (IC50 = 7 and 5 mu M, respectively), which was comparable with liarozole (7 mu M) but considerably less active than R115866 (IC50 = 5 nM). With a CYP26A1 homology model, the tetralones were shown to be positioned in a hydrophobic tunnel with additional interactions, e.g., transition metal coordination and hydrogen-bonding interactions with GLY300, observed for the potent 4-hydroxyphenyl substituted inhibitors.