7-[(3-bromobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one | 1522346-60-6

• 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-[(3-bromobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one
• 英文别名: 7-[(3-Bromophenyl)methoxy]-4-(chloromethyl)chromen-2-one；7-[(3-bromophenyl)methoxy]-4-(chloromethyl)chromen-2-one
• CAS: 1522346-60-6
• 化学式: C₁₇H₁₂BrClO₃
• 分子量: 379.637
• InChiKey: GCVQPKZTIVRHFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.87
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  39.44
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  7-[(3-bromobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one 在 水 作用下， 反应 48.0h， 以46%的产率得到7-[(3-bromobenzyl)oxy]-4-(hydroxymethyl)-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：

  间苯二酚 在 硫酸 、 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 生成 7-[(3-bromobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one
  参考文献：
  名称：

  追逐 ChEs-MAO B 多靶点 4-氨甲基-7-苄氧基-2H-Chromen-2-酮

  摘要：

  研究了一系列 4-氨甲基-7-苄氧基-2H-色烯-2-酮，旨在鉴定多种胆碱酯酶（乙酰基和丁酰基、AChE 和 BChE）和单胺氧化酶 B (MAO B) 的潜在抑制剂抗阿尔茨海默病分子。从先前报道的有效 MAO B 抑制剂 (3) 开始，我们研究了苄氧基或碱性部分的单点修饰。体外筛选突出显示了三效化合物 (6、8、9、16、20)，显示出纳摩尔级选择性 MAO B 抑制作用以及低微摩尔水平下针对 ChE 的 IC50 值。对 AChE 进行酶动力学分析并对目标酶进行对接模拟，以深入了解作用机制和合理的结合模式。

  DOI：

  10.3390/molecules24244507

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.
• Chasing ChEs-MAO B Multi-Targeting 4-Aminomethyl-7-Benzyloxy-2H-Chromen-2-ones
  作者：Mariagrazia Rullo、Marco Catto、Antonio Carrieri、Modesto de Candia、Cosimo Damiano Altomare、Leonardo Pisani

  DOI：10.3390/molecules24244507

  日期：——

  multiple inhibitors of cholinesterases (acetyl- and butyryl-, AChE and BChE) and monoamine oxidase B (MAO B) as potential anti-Alzheimer molecules. Starting from a previously reported potent MAO B inhibitor (3), we studied single-point modifications at the benzyloxy or at the basic moiety. The in vitro screening highlighted triple-acting compounds (6, 8, 9, 16, 20) showing nanomolar and selective MAO B inhibition

  研究了一系列 4-氨甲基-7-苄氧基-2H-色烯-2-酮，旨在鉴定多种胆碱酯酶（乙酰基和丁酰基、AChE 和 BChE）和单胺氧化酶 B (MAO B) 的潜在抑制剂抗阿尔茨海默病分子。从先前报道的有效 MAO B 抑制剂 (3) 开始，我们研究了苄氧基或碱性部分的单点修饰。体外筛选突出显示了三效化合物 (6、8、9、16、20)，显示出纳摩尔级选择性 MAO B 抑制作用以及低微摩尔水平下针对 ChE 的 IC50 值。对 AChE 进行酶动力学分析并对目标酶进行对接模拟，以深入了解作用机制和合理的结合模式。