3-((4-methoxybenzyl)oxy)-2-methyl-4H-pyran-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-((4-methoxybenzyl)oxy)-2-methyl-4H-pyran-4-one
• 英文别名: 2-methyl-3-p-methoxybenzyloxypyran-4-one；3-[(4-Methoxyphenyl)methoxy]-2-methylpyran-4-one
• 化学式: C₁₄H₁₄O₄
• 分子量: 246.263
• InChiKey: KNPDMBZTWWRBTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  3-((4-methoxybenzyl)oxy)-2-methyl-4H-pyran-4-one 在 4-二甲氨基吡啶 、 三氯化硼 、 2-巯基噻唑啉 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 61.5h， 生成 N-(2-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl)-7-((4-methoxybenzyl)oxy)-2-oxo-2H-chromene-3-carboxamide
  参考文献：
  名称：

  Rational design, synthesis and biological evaluation of novel multitargeting anti-AD iron chelators with potent MAO-B inhibitory and antioxidant activity

  摘要：

  A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multi targeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe(3+) values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC50 value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid-beta(1-42) (A beta(1-42)) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.

  DOI：

  10.1016/j.bmc.2020.115550
• 作为产物：
  描述：

  麦芽醇 、 4-甲氧基氯苄 在 potassium carbonate 作用下， 反应 2.0h， 生成 3-((4-methoxybenzyl)oxy)-2-methyl-4H-pyran-4-one
  参考文献：
  名称：

  发现苯甲酰胺-羟基吡啶酮杂化物作为治疗阿尔茨海默病的有效多靶点药物

  摘要：

  摘要 通过基于先导化合物18d、苄氧基苯基类似物和去铁酮的药效团合并方法，创新地设计、合成和生物学评估了一类新的苯甲酰胺-羟基吡啶酮 (HPO) 衍生物作为治疗阿尔茨海默病 (AD) 的潜在多靶点候选药物(DFP)。这些杂种具有有效的单胺氧化酶 B (MAO-B) 抑制作用以及出色的铁螯合性，pFe 3+值范围为 18.13 至 19.39。在所有化合物中，8g表现出最有效的选择性 MAO-B 抑制剂（IC 50 = 68.4 nM，SI = 213）。此外，8g显示出良好的药代动力学特性，并具有巨大的穿透 BBB 的潜力计算机和 PAMPA-BBB 测定。分子模型表明，8g可以采用扩展构象，并且与 MAO-B 的相互作用比18d更强。体外和体内试验表明，8g显着抵抗 Aβ 诱导的氧化并改善东莨菪碱诱导的认知障碍。综上所述，这些结果表明化合物8g是一种潜在的多功能抗 AD 治疗候选药物。

  DOI：

  10.1080/14756366.2021.1978081

文献信息

• 具潜在多靶点抗AD活性的甲酰胺吡啶酮类铁螯合剂衍生物及其制备方法与应用
  申请人：浙江工业大学

  公开号：CN111995567B

  公开（公告）日：2022-11-25

  本发明提供了一种式(I)或式(II)所示的甲酰胺吡啶酮类铁螯合剂衍生物及其制备方法与应用；所述式(I)或式(II)所示的甲酰胺吡啶酮类铁螯合剂衍生物及其药学上可接受的盐具有抑制单胺氧化酶、螯合金属铁离子、抗Aβ及抗氧化活性，可用于制备抗阿尔兹海默症、抗帕金森病或通过抑制单胺氧化酶、螯合金属铁离子、抗Aβ及抗氧化来治疗的其它病症的药物；
• Cephem compounds compositions and method
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05438053A1

  公开（公告）日：1995-08-01

  Novel cephem compounds having, at the 3-position of the cephem nucleus, a group of the formula: --CH.sub.2 --S--A--Y--B wherein A stands for a further optionally substituted divalent nonionic aromatic heterocyclic group bounded to the adjacent sulfur atom via carbon atom, Y stands for a bond, a sulfur atom, an oxygen atom, NH, CONH, SO.sub.2 NH or a divalent C.sub.1 -C.sub.6 hydrocarbon chain optionally including one or two selected from the group consisting of sulfur atom, oxygen atom, NH group, CONH group and SO.sub.2 NH group in the chain, and B stands for a group of the formula: ##STR1## wherein R.sup.3 stands for H or an optionally substituted lower alkyl, R.sup.4 and R.sup.4 ' each stand for H, OH, an optionally substituted lower alkyl, COOH or CONH, or salts thereof, having excellent antibacterial activities especially against Pseudomonas aeruginosa and keeping effective serum levels over a long period.

  新型头孢烯化合物，其在头孢烯核的3位上具有以下通式所示的基团：--CH.sub.2 --S--A--Y--B，其中A代表通过碳原子与相邻硫原子相连的可选取代的二价非离子性芳香杂环基团，Y代表键、硫原子、氧原子、NH、CONH、SO.sub.2 NH或可选包含一个或两个选自硫原子、氧原子、NH基团、CONH基团和SO.sub.2 NH基团的二价C.sub.1 -C.sub.6烃链，B代表以下通式所示的基团：##STR1##其中R.sup.3代表H或可选取代的低级烷基，R.sup.4和R.sup.4'各自代表H、OH、可选取代的低级烷基、COOH或CONH，或其盐，具有优异的抗菌活性，特别是对铜绿假单胞菌，并能长时间维持有效的血清水平。
• Study of Iron Piperazine-Based Chelators as Potential Siderophore Mimetics
  作者：Loupias、Dechamps-Olivier、Dupont、Vanlemmens、Mullié、Taudon、Bouchut、Dassonville-Klimpt、Sonnet

  DOI：10.3390/ph12040160

  日期：——

  Gram-negative bacteria’s resistance such as Pseudomonas aeruginosa and the Burkholderia group to conventional antibiotics leads to therapeutic failure. Use of siderophores as Trojan horses to internalize antibacterial agents or toxic metals within bacteria is a promising strategy to overcome resistance phenomenon. To combat the Pseudomonas sp, we have synthesized and studied two piperazine-based siderophore mimetics carrying either catecholate moieties (1) or hydroxypyridinone groups (2) as iron chelators. These siderophore-like molecules were prepared in no more than four steps with good global yields. The physicochemical study has highlighted a strong iron affinity since their pFe values were higher than 20. 1 possesses even a pFe value superior than those of pyoverdine, the P. aeruginosa endogenous siderophore, suggesting its potential ability to compete with it. At physiological pH, 1 forms mainly a 2:3 complex with iron, whereas two species are observed for 2. Unfortunately, the corresponding Ga(III)-1 and 2 complexes showed no antibacterial activity against P. aeruginosa DSM 1117 strain. The evaluation of their siderophore-like activity showed that 1 and 2 could be internalized by the bacteria.

  革兰氏阴性细菌的抗药性，如铜绿假单胞菌和伯克霍尔德菌群对传统抗生素的抵抗导致治疗失败。利用铁载体作为特洛伊木马将抗菌剂或有毒金属内化到细菌内部是克服抵抗现象的一种有前景的策略。为了对抗铜绿假单胞菌，我们合成并研究了两种基于哌嗪的铁载体模拟物，分别携带邻苯二酚基团（1）或羟基吡啶酮基团（2）作为铁螯合剂。这些类似铁载体的分子在不超过四个步骤中制备，全球产率良好。物理化学研究强调了它们与铁的亲和力很强，因为它们的pFe值高于20。1甚至具有比铜绿假单胞菌内源性铁载体吡沃德因更高的pFe值，表明它有潜力与之竞争。在生理pH下，1主要形成与铁的2:3络合物，而2观察到两种物种。不幸的是，对应的Ga(III)-1和2络合物对铜绿假单胞菌DSM 1117菌株没有抗菌活性。它们的类似铁载体活性评估表明1和2可以被细菌内化。
• 具潜在抗AD活性的香豆素杂合吡啶酮酰胺衍 生物及其制备方法与应用
  申请人：浙江工业大学

  公开号：CN110804045B

  公开（公告）日：2021-07-27

  本发明公开了一种香豆素杂合吡啶酮酰胺衍生物及其制备方法与应用。所述的香豆素杂合吡啶酮酰胺衍生物及其药学上可接受的盐如式(I)或式(II)所示，其可应用于制备抗阿尔兹海默症、抗帕金森病或通过抑制单胺氧化酶、螯合金属铁离子、抗Aβ及抗氧化来治疗的其它疾病或病症药物方面的用途。
• Chromone-based monoamine oxidase B inhibitor with potential iron-chelating activity for the treatment of Alzheimer’s disease
  作者：Changjun Zhang、Yujia Zhang、Yangjing Lv、Jianan Guo、Bianbian Gao、Yi Lu、Anjie Zang、Xi Zhu、Tao Zhou、Yuanyuan Xie

  DOI：10.1080/14756366.2022.2134358

  日期：2023.12.31

  hybrids were designed, synthesised, and evaluated as potential multimodal anti-AD ligands. Prospective iron-chelating effects and favourable monoamine oxidase B (MAO-B) inhibitory activities were observed for most of the compounds. Pharmacological assays led to the identification of compound 17d, which exhibited favourable iron-chelating potential (pFe3+ = 18.52) and selective hMAO-B inhibitory activity

  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。