7-(2-bromoethoxy)-4-methoxy-2H-chromen-2-one | 1314133-72-6

• 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: 7-(2-bromoethoxy)-4-methoxy-2H-chromen-2-one
• 英文别名: 7-(2-Bromoethoxy)-4-methoxychromen-2-one；7-(2-bromoethoxy)-4-methoxychromen-2-one
• CAS: 1314133-72-6
• 化学式: C₁₂H₁₁BrO₄
• 分子量: 299.121
• InChiKey: BYOBXVODWUKXRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-甲氧基苯基)哌嗪 、 7-(2-bromoethoxy)-4-methoxy-2H-chromen-2-one 在 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 48.0h， 以37%的产率得到4-methoxy-7-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethoxy}-2H-chromen-2-one
  参考文献：
  名称：

  香豆素衍生物作为α1-肾上腺素受体拮抗剂的合理设计，合成，生物学评估，同源性和对接研究。

  摘要：

  根据一些尿液选择性α（1）肾上腺素能受体（AR）拮抗剂的三点药效基团，已经成功设计并合成了新型香豆素（= 2H-1-苯并吡喃-2-酮）衍生物。对于α（1）-AR。这些合成的香豆素衍生物在体外药理试验中显示出对α（1）-AR的高效率。与哌唑嗪相比（pK（i）值为8.77），在这些香豆素中，甲苯​​基哌嗪取代的衍生物7和8的pK（i）值分别为8.81和8.77。这些香豆素衍生物对α（1A）-肾上腺素受体的功效趋势通过密集的分子对接进一步合理化。我们的工作表明，设计的香豆素衍生物可以在体外抑制α（1）-AR。

  DOI：

  10.1002/cbdv.201000135
• 作为产物：
  描述：

  间苯二酚 在 硫酸 、 potassium carbonate 、 zinc(II) chloride 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 49.5h， 生成 7-(2-bromoethoxy)-4-methoxy-2H-chromen-2-one
  参考文献：
  名称：

  香豆素衍生物作为α1-肾上腺素受体拮抗剂的合理设计，合成，生物学评估，同源性和对接研究。

  摘要：

  根据一些尿液选择性α（1）肾上腺素能受体（AR）拮抗剂的三点药效基团，已经成功设计并合成了新型香豆素（= 2H-1-苯并吡喃-2-酮）衍生物。对于α（1）-AR。这些合成的香豆素衍生物在体外药理试验中显示出对α（1）-AR的高效率。与哌唑嗪相比（pK（i）值为8.77），在这些香豆素中，甲苯​​基哌嗪取代的衍生物7和8的pK（i）值分别为8.81和8.77。这些香豆素衍生物对α（1A）-肾上腺素受体的功效趋势通过密集的分子对接进一步合理化。我们的工作表明，设计的香豆素衍生物可以在体外抑制α（1）-AR。

  DOI：

  10.1002/cbdv.201000135

文献信息

• Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease
  作者：Sai-Sai Xie、Xiaobing Wang、Neng Jiang、Wenying Yu、Kelvin D.G. Wang、Jin-Shuai Lan、Zhong-Rui Li、Ling-Yi Kong

  DOI：10.1016/j.ejmech.2015.03.040

  日期：2015.5

  A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BuChE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BuChE (IC50 values of 80.72 nM for eqBuChE and 112.72 nM for hBuChE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 mu M). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Design, synthesis and evaluation of novel tacrine–coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease
  作者：Sai-Sai Xie、Xiao-Bing Wang、Jiang-Yan Li、Lei Yang、Ling-Yi Kong

  DOI：10.1016/j.ejmech.2013.03.051

  日期：2013.6

  A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced,beta-amyloid (A beta) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 mu M) and A beta aggregation (67.8%, 20 mu M). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 mu M) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Design, synthesis and biological evaluation of novel donepezil–coumarin hybrids as multi-target agents for the treatment of Alzheimer’s disease
  作者：Sai-Sai Xie、Jin-Shuai Lan、Xiaobing Wang、Zhi-Min Wang、Neng Jiang、Fan Li、Jia-Jia Wu、Jin Wang、Ling-Yi Kong

  DOI：10.1016/j.bmc.2016.02.023

  日期：2016.4

  Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87 mu M and 0.93 mu M, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37 mu M for hAChE; 1.98 mu M for hBuChE; 2.62 mu M for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit. (C) 2016 Elsevier Ltd. All rights reserved.
• Rational Design, Synthesis, Biological Evaluation, Homology and Docking Studies of Coumarin Derivatives as α1-Adrenoceptor Antagonists
  作者：Xiang Zhou、Ya-Dong Chen、Tao Wang、Xiao-Bing Wang、Ling-Yi Kong

  DOI：10.1002/cbdv.201000135

  日期：2011.6

  -adrenoceptor (AR) antagonists, a novel class of coumarin (=2H-1-benzopyran-2-one) derivatives have been successfully designed and synthesized with high efficacies for α(1) -AR. These synthesized coumarin derivatives exhibited high efficacies towards α(1) -AR in in vitro pharmacological assays. Compared with prazosin (pK(i) value of 8.77), among those coumarins, tolylpiperazine-substituted derivatives, 7 and 8

  根据一些尿液选择性α（1）肾上腺素能受体（AR）拮抗剂的三点药效基团，已经成功设计并合成了新型香豆素（= 2H-1-苯并吡喃-2-酮）衍生物。对于α（1）-AR。这些合成的香豆素衍生物在体外药理试验中显示出对α（1）-AR的高效率。与哌唑嗪相比（pK（i）值为8.77），在这些香豆素中，甲苯​​基哌嗪取代的衍生物7和8的pK（i）值分别为8.81和8.77。这些香豆素衍生物对α（1A）-肾上腺素受体的功效趋势通过密集的分子对接进一步合理化。我们的工作表明，设计的香豆素衍生物可以在体外抑制α（1）-AR。