1-(4-((3-chlorobenzyl)oxy)-2-hydroxyphenyl)ethanone | 1522345-37-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-((3-chlorobenzyl)oxy)-2-hydroxyphenyl)ethanone
• 英文别名: 1-[4-[(3-Chlorophenyl)methoxy]-2-hydroxyphenyl]ethanone；1-[4-[(3-chlorophenyl)methoxy]-2-hydroxyphenyl]ethanone
• CAS: 1522345-37-4
• 化学式: C₁₅H₁₃ClO₃
• 分子量: 276.719
• InChiKey: JPPWJTVYLPMANA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.83
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(4-((3-chlorobenzyl)oxy)-2-hydroxyphenyl)ethanone 在 ammonium acetate 、 sodium 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 生成 4-amino-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：

  2,4-二羟基苯乙酮 、 3-氯苄溴 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以70 %的产率得到1-(4-((3-chlorobenzyl)oxy)-2-hydroxyphenyl)ethanone
  参考文献：
  名称：

  基于色酮的单胺氧化酶 B 抑制剂，具有潜在的铁螯合活性，用于治疗阿尔茨海默病

  摘要：

  摘要 基于多靶点定向配体 (MTDLs) 策略，设计、合成并评估了一系列色酮-羟基吡啶酮杂化物作为潜在的多峰抗 AD 配体。大多数化合物都具有预期的铁螯合作用和有利的单胺氧化酶 B (MAO-B) 抑制活性。药理学分析鉴定出化合物17d，它表现出良好的铁螯合潜力 (pFe 3+ = 18.52) 和选择性h MAO-B 抑制活性（IC 50 = 67.02 ± 4.3 nM，SI = 11）。对接模拟表明，17d占据了 MAO-B 的底物和入口腔，并与口袋残基建立了几个关键的相互作用。而且，17d被确定可以穿过血脑屏障 (BBB)，并且可以显着改善东莨菪碱诱导的 AD 小鼠认知障碍。尽管其药代动力学特性不理想，但17d仍然是一种有前途的多方面药物，值得进一步研究。

  DOI：

  10.1080/14756366.2022.2134358

文献信息

• Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson’s disease
  作者：Zhimin Wang、Jiajia Wu、Xuelian Yang、Pei Cai、Qiaohong Liu、Kelvin D.G. Wang、Lingyi Kong、Xiaobing Wang

  DOI：10.1016/j.bmc.2016.09.050

  日期：2016.11

  The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson’s disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA-

  苄氧基取代的小分子是众所周知的高效单胺氧化酶B抑制剂，但尚未详细研究其对帕金森氏病的治疗潜力。在本文中，合成了一系列代表性的苄氧基取代的衍生物，并评估了对MAO-A / B的抑制作用。此外，在6-OHDA和鱼藤酮处理的PC12细胞中研究了它们的神经保护作用。观察到，大多数化合物在用神经毒素处理的PC12细胞的存活率中显示出明显的增加。其中，有13种表现出显着且平衡的神经保护效能。流式细胞术和染色方法证实了13对神经毒素诱导的细胞凋亡的保护作用。此外，根据体外BBB预测和体内急性毒性试验，13还显示出良好的BBB通透性和低毒性。结果表明13是有效和有希望的候选者，可以进一步开发作为帕金森氏病治疗的疾病缓解药物。
• 具有潜在铁螯合活性的单胺氧化酶B抑制剂及其应用
  申请人：浙江工业大学

  公开号：CN114149417A

  公开（公告）日：2022-03-08

  本发明合成了一类具有铁离子螯合活性的单胺氧化酶抑制剂，创新性地将具有铁离子螯合活性的吡啶酮衍生物与具有MAO‑B抑制活性的色酮母核有机结合在一起，对于发病机制复杂的阿尔茨海默症以及帕金森等神经退行性疾病具有显著优势。
• Synthesis of 4-substituted benzyl-2-triazole-linked-tryptamine-paeonol derivatives and evaluation of their selective inhibitions against butyrylcholinesterase and monoamine oxidase-B
  作者：Jong Min Oh、Yujung Kang、Ji Hyun Hwang、Jeong-Ho Park、Woong-Hee Shin、Seul-Ki Mun、Jong Uk Lee、Sung-Tae Yee、Hoon Kim

  DOI：10.1016/j.ijbiomac.2022.07.178

  日期：2022.9

  Cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors are being used and developed to treat Alzheimer's disease (AD), a major type of dementia patients. Fifteen 4-substituted benzyl-2-triazole-linked-tryptamine-paeonol derivatives were synthesized and evaluated for their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase-A (MAO-A), and B (MAO-B)

  胆碱酯酶 （ChE） 和单胺氧化酶 （毛） 抑制剂正在被用于和开发用于治疗阿尔茨海默病 （AD），这是一种主要的痴呆患者。合成了 15 种 4-取代的苄基-2-三唑连接的色胺-丹皮醇衍生物，并评价了它们对乙酰胆碱酯酶 （AChE）、丁酰胆碱酯酶 （BChE）、单胺氧化酶-A （毛-A） 和 B （毛-B） 的抑制活性。化合物 896 是最有效的 BChE 抑制剂 （IC50 = 0.13 μM），对 BChE 的选择性指数 （SI） 值为 >769.23 优于 AChE。化合物 897 是最有效的选择性 毛-B 抑制剂 （IC50 = 0.73 μM;SI = 20.45 对于 毛-B 超过 毛-A）。896 的 meta-CF3 取代基增加了 BChE 抑制活性，897 的 para-CF3 取代基增加了 毛-B 抑制活性。化合物 896 是一种可逆的非竞争性 BChE 抑制剂 （Ki =
• 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors
  作者：Lesetja Legoabe、Jacobus Petzer、Anél Petzer

  DOI：10.2147/dddt.s86225

  日期：——

  Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO) inhibitors, a series of C5-substituted 2-acetylphenol analogs (15) and related compounds (two) were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values <0.01 mu M for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure-activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson's disease.
• 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.