1-{4-[(3-bromobenzyl)oxy]-2-hydroxyphenyl}ethanone | 1393374-51-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-{4-[(3-bromobenzyl)oxy]-2-hydroxyphenyl}ethanone
• 英文别名: 2-acetyl-5-(3-bromobenzyloxy)phenol；1-[4-[(3-Bromophenyl)methoxy]-2-hydroxyphenyl]ethanone
• CAS: 1393374-51-0
• 化学式: C₁₅H₁₃BrO₃
• 分子量: 321.17
• InChiKey: KWTLOPBWGVZIHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 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：

  1-{4-[(3-bromobenzyl)oxy]-2-hydroxyphenyl}ethanone 在 sodium 、 potassium carbonate 作用下， 以 丁酮 为溶剂， 反应 4.0h， 生成 ethyl ({7-[(3-bromobenzyl)oxy]-2-oxo-2H-chromen-4-yl}oxy)acetate
  参考文献：
  名称：

  Fine molecular tuning at position 4 of 2H-chromen-2-one derivatives in the search of potent and selective monoamine oxidase B inhibitors

  摘要：

  The effects on the inhibition potencies of monoamine oxidase isoforms A (MAO-A) and B (MAO-B) depending upon changes in the physicochemical properties (size, shape, H-bonding, lipophilicity, etc.) of substituents at the C4 position of 2H-chromen-2-one derivatives were extensively investigated, and the results significantly added to our knowledge on this class of MAO inhibitors. All the 67 examined compounds showed high MAO-B selectivity, some of them achieving potency in the low nanomolar range. In particular, the 7-metachlorobenzyloxy-4-oxyacetamido-211-chromen-2-one (entry 62) showed single digit nanomolar MAO-B potency (IC50 = 3.1 nM) and high selectivity over the MAO-A isoform (selectivity ratio = 7244). The great variety of the investigated substituents at C4 of the 2H-chromen-2-one nucleus, combined with binding models generated from docking studies carried out on selected compounds, allowed us to shed light on the main molecular requirements for potent and selective MAO-B inhibition, highlighting the dominant role of the steric effects. Interestingly, many of the designed substituents could be metabolically related to each other (e.g., CH3/CH2OH/CHO/COOH; NH2/NHCH3, NHAc), and therefore the results obtained may help in predicting the in vivo activity of some putative metabolites of lead MAO-B inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.034
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 、 3-溴苄溴 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 8.0h， 以89%的产率得到1-{4-[(3-bromobenzyl)oxy]-2-hydroxyphenyl}ethanone
  参考文献：
  名称：

  Selected chromone derivatives as inhibitors of monoamine oxidase

  摘要：

  A previous study has shown that a series of C6-benzyloxy substituted chromones exhibit high binding affinities for human monoamine oxidase (MAO) B. In an attempt to discover additional chromones with potent and selective MAO-B inhibitory potencies and to further examine the structure-activity relationships of MAO-B inhibition by chromones, the series was expanded with homologues containing polar functional groups on C3 of the chromone ring. The results demonstrate that 6-[(3-bromobenzyl)oxy] chromones containing acidic and aldehydic functional groups on C3 act as potent reversible MAO-B inhibitors with IC50 values of 2.8 and 3.7 nM, respectively. Interestingly, a 2-hydroxy-2,3-dihydro-1-benzopyran-4-one derivative as well as open-ring 2-acetylphenol analogues of the chromones also were potent MAO-B inhibitors with IC50 values ranging from 4 to 11 nM. Chromone derivatives containing the benzyloxy substituent on C5 of the chromone ring, however, exhibit MAO-B inhibition potencies that are several orders of magnitude weaker. High potency inhibitors of MAO-B may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.025

文献信息

• Fine molecular tuning at position 4 of 2H-chromen-2-one derivatives in the search of potent and selective monoamine oxidase B inhibitors
  作者：Leonardo Pisani、Marco Catto、Orazio Nicolotti、Giancarlo Grossi、Mario Di Braccio、Ramon Soto-Otero、Estefania Mendez-Alvarez、Angela Stefanachi、Domenico Gadaleta、Angelo Carotti

  DOI：10.1016/j.ejmech.2013.09.034

  日期：2013.12

  The effects on the inhibition potencies of monoamine oxidase isoforms A (MAO-A) and B (MAO-B) depending upon changes in the physicochemical properties (size, shape, H-bonding, lipophilicity, etc.) of substituents at the C4 position of 2H-chromen-2-one derivatives were extensively investigated, and the results significantly added to our knowledge on this class of MAO inhibitors. All the 67 examined compounds showed high MAO-B selectivity, some of them achieving potency in the low nanomolar range. In particular, the 7-metachlorobenzyloxy-4-oxyacetamido-211-chromen-2-one (entry 62) showed single digit nanomolar MAO-B potency (IC50 = 3.1 nM) and high selectivity over the MAO-A isoform (selectivity ratio = 7244). The great variety of the investigated substituents at C4 of the 2H-chromen-2-one nucleus, combined with binding models generated from docking studies carried out on selected compounds, allowed us to shed light on the main molecular requirements for potent and selective MAO-B inhibition, highlighting the dominant role of the steric effects. Interestingly, many of the designed substituents could be metabolically related to each other (e.g., CH3/CH2OH/CHO/COOH; NH2/NHCH3, NHAc), and therefore the results obtained may help in predicting the in vivo activity of some putative metabolites of lead MAO-B inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Selected chromone derivatives as inhibitors of monoamine oxidase
  作者：Lesetja J. Legoabe、Anél Petzer、Jacobus P. Petzer

  DOI：10.1016/j.bmcl.2012.07.025

  日期：2012.9

  A previous study has shown that a series of C6-benzyloxy substituted chromones exhibit high binding affinities for human monoamine oxidase (MAO) B. In an attempt to discover additional chromones with potent and selective MAO-B inhibitory potencies and to further examine the structure-activity relationships of MAO-B inhibition by chromones, the series was expanded with homologues containing polar functional groups on C3 of the chromone ring. The results demonstrate that 6-[(3-bromobenzyl)oxy] chromones containing acidic and aldehydic functional groups on C3 act as potent reversible MAO-B inhibitors with IC50 values of 2.8 and 3.7 nM, respectively. Interestingly, a 2-hydroxy-2,3-dihydro-1-benzopyran-4-one derivative as well as open-ring 2-acetylphenol analogues of the chromones also were potent MAO-B inhibitors with IC50 values ranging from 4 to 11 nM. Chromone derivatives containing the benzyloxy substituent on C5 of the chromone ring, however, exhibit MAO-B inhibition potencies that are several orders of magnitude weaker. High potency inhibitors of MAO-B may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. (C) 2012 Elsevier Ltd. All rights reserved.