7-[(3-chlorobenzyl)oxy]-4-(1-hydroxyethyl)-2H-1-benzopyran-2-one | 1522346-74-2

• 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-[(3-chlorobenzyl)oxy]-4-(1-hydroxyethyl)-2H-1-benzopyran-2-one
• 英文别名: 7-[(3-Chlorophenyl)methoxy]-4-(1-hydroxyethyl)chromen-2-one；7-[(3-chlorophenyl)methoxy]-4-(1-hydroxyethyl)chromen-2-one
• CAS: 1522346-74-2
• 化学式: C₁₈H₁₅ClO₄
• 分子量: 330.768
• InChiKey: DETWBNHUPBJSGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-[(3-chlorobenzyl)oxy]-4-(1-hydroxyethyl)-2H-1-benzopyran-2-one 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以46%的产率得到4-acetyl-7-[(3-chlorobenzyl)oxy]-2H-chromen-2-one
  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：

  4-乙基-7-羟基香豆素 在 selenium(IV) oxide 、 sodium ethanolate 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 为溶剂， 反应 5.0h， 生成 7-[(3-chlorobenzyl)oxy]-4-(1-hydroxyethyl)-2H-1-benzopyran-2-one
  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

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.