3-羟基-7-甲氧基-2H-色烯-2-酮 | 33265-12-2

• 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
• 中文名称: 3-羟基-7-甲氧基-2H-色烯-2-酮
• 英文名称: 3-hydroxy-7-methoxy-2H-chromen-2-one
• 英文别名: 3-hydroxy-7-methoxy-chromen-2-one；3-Hydroxy-7-methoxycumarin；3-Hydroxy-7-methoxychromen-2-one
• CAS: 33265-12-2
• 化学式: C₁₀H₈O₄
• 分子量: 192.171
• InChiKey: XAKPXVHELMEQCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 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：

  3-羟基-7-甲氧基-2H-色烯-2-酮 在 camphor-10-sulfonic acid 、 三氟化硼乙醚 作用下， 以 甲苯 为溶剂， 反应 42.0h， 生成 7-Methoxy-4-methyl-9-oxa-1-aza-phenanthren-10-one
  参考文献：
  名称：

  Pavé, Grégoire; Chalard, Pierre; Viaud-Massuard, Marie-Claude, Synlett, 2003, # 7, p. 987 - 990

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(7-methoxy-2-oxo-2H-chromen-3-yl)acetamide 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 10.0h， 以74%的产率得到3-羟基-7-甲氧基-2H-色烯-2-酮
  参考文献：
  名称：

  致力于针对布鲁氏锥虫和克氏锥虫的双靶向甘油醛-3-磷酸脱氢酶/锥虫硫醇还原酶抑制剂的开发

  摘要：

  硝呋替莫–氟鸟氨酸联合疗法（NECT）的最新开发已实现了锥虫病治疗的显着改善。作为药物组合的替代方法和克服大多数抗锥虫病药物发现挑战的方法，已经设想了多目标药物设计策略。为了开始验证该假设，我们设计并开发了一系列针对3-磷酸甘油醛脱氢酶/锥虫硫酮还原酶（GAPDH / TR）的醌-香豆素杂种。这些酶属于对布鲁氏锥虫和克氏锥虫至关重要的代谢途径，因此被认为是有前途的药物靶标。合成的分子在酶测定和体外寄生虫培养中均具有双重靶点抗锥虫体特征。合并后的衍生物：2 - {[3-（3-二甲氨基丙氧基）-2-氧代-2- ħ -苯并吡喃-7-基]氧基}蒽-1,4-二酮（10）表现出的IC 50为5.4值μ中号对铽GAPDH和伴随ķ我的2.32值μ中号对锝TR。值得注意的是，2- {4- [6- [2-（2-二甲基氨基乙氧基）-2-oxo-2 H-铬n-3-基]苯氧基}蒽-1,4-二酮（化合物6）表现出了卓越的EC

  DOI：

  10.1002/cmdc.201300399

文献信息

• A novel class of human 15-LOX-1 inhibitors based on 3-hydroxycoumarin
  作者：Seyed Jamal Alavi、Hamid Sadeghian、Seyed Mohammad Seyedi、Alireza Salimi、Hossein Eshghi

  DOI：10.1111/cbdd.13174

  日期：2018.6

  Owing to the importance of these enzymes, mechanistic studies, product analysis, and synthesis of inhibitors have expanded. In this study, a series of hydroxycoumarins, methoxy‐3‐hydroxy coumarins, and 7‐alkoxy‐3‐hydroxy coumarins were synthesized and evaluated as potential inhibitors of human 15‐LOX‐1. Among the synthetic coumarins, 7‐methoxy‐3‐hydroxycoumarin derivative demonstrated potent inhibitory

  哺乳动物的炎症，敏感性和某些癌症与脂氧合酶的活性密切相关。由于这些酶的重要性，机理研究，产物分析和抑制剂的合成得到了扩展。在这项研究中，合成了一系列羟基香豆素，甲氧基-3-羟基香豆素和7-烷氧基-3-羟基香豆素，并将其评估为人类15-LOX-1的潜在抑制剂。在合成香豆素中，7-甲氧基-3-羟基香豆素衍生物显示出有效的抑制活性，化合物5f显示出最佳的抑制效果。自由基清除评估，IC 50，HNMR和DPPH漂白结果表明，电子性能是合成香豆素抑制脂加氧酶效能的主要因素。根据理论研究，有人提出苯环第七位取代基的介观效应是氧自由基中间体稳定性的主要因素之一。
• Reaction of aryl-2-hydroxypropenoic derivatives with boron tribromide
  作者：Romain Dupont、Philippe Cotelle

  DOI：10.1016/s0040-4039(00)02011-6

  日期：2001.1

  trimethoxyphenyl-2-hydroxypropenoic acids 1a–d gave mixtures of (E) and (Z) mono, di or trihydroxyphenyl-2-hydroxypropenoic acids 2a–d when treated with boron tribromide. The isomerisation proceeds during the work-up and depends on the duration of the hydrolysis and the number of oxygens on the aromatic ring. When the aromatic ring was substituted with a methoxy group at the ortho position, a cyclisation occurs

  （Ž） -单，二或三甲氧基苯基-2- hydroxypropenoic酸1A-d得到（的混合物ë）和（Ž）单，二或三羟基苯基-2- hydroxypropenoic酸图2a-d时用三溴化硼。异构化在后处理过程中进行，并取决于水解的持续时间和芳环上的氧数。当芳环在邻位被甲氧基取代时，发生环化，并且可以获得3-羟基香豆素3和苯并呋喃-2-羧酸4。3-羟基香豆素3a 3-（2-甲氧基苯基）-2，3-环氧丙酸甲酯与三溴化硼的反应也几乎可以定量获得。
• Inhibition of iNOS by Benzimidazole Derivatives: Synthesis, Docking, and Biological Evaluations
  作者：Yogita Bansal、Richa Minhas

  DOI：10.2174/1573406417666210927123137

  日期：2022.5

  Inducible nitric Oxide Synthase (iNOS) plays a key role in the progression of inflammatory diseases by accelerating the production of NO, which makes it an intriguing target to treat inflammation in complex diseases. Therefore, the search is on to develop molecules as selective iNOS inhibitors.

  The present work was aimed to design, synthesize and evaluate benzimidazole-coumarin coupled molecules as anti-iNOS agents through in silico and pharmacological studies.

  A critical study of literature reports on iNOS inhibitors led to the selection of a (un)substituted coumarin nucleus, 2-aminobenzimidazole, and a 4-atom linker as important structural components for iNOS inhibition. Two series of compounds (7-16 and 17-26) were designed and synthesized by coupling these components. The compounds were subjected to docking using iNOS (1QW4) and nNOS (1QW6) as targets. All compounds were evaluated for NO and iNOS inhibitory activities in vitro. The selected compound was finally evaluated for anti-inflammatory activity in vivo using the carrageenan-induced rat paw edema model.

  All compounds showed moderate to good inhibition of NO and iNOS in vitro. Compound 12 was the most potent inhibitor of NO and iNOS. Hence, it was evaluated in vivo for toxicity and anti-inflammatory activity. It was found to be safe in acute toxicity studies, and effective in reducing the rat paw edema significantly. Its anti-inflammatory behaviour was similar to that of aminoguanidine, which is a selective iNOS inhibitor.

  The newly synthesized benzimidazole-coumarin hybrids may serve as potential leads for the development of novel anti-iNOS agents.

  背景：可诱导型一氧化氮合酶（iNOS）通过加速NO的产生在炎症性疾病的进展中发挥关键作用，因此，寻找开发选择性iNOS抑制剂的分子成为治疗复杂疾病炎症的有趣目标。 目的：本研究旨在通过计算机模拟和药理学研究设计、合成和评价苯并咪唑-香豆素偶联分子作为抗iNOS剂。 方法：对iNOS抑制剂的文献报告进行了关键研究，选择了（不）取代的香豆素核、2-氨基苯并咪唑和4原子连接器作为iNOS抑制的重要结构组成部分。设计并合成了两个系列的化合物（7-16和17-26）通过耦合这些组分。将这些化合物作为靶点进行iNOS（1QW4）和nNOS（1QW6）的对接。所有化合物均在体外评估了NO和iNOS的抑制活性。最终选定的化合物通过使用卡拉蓝诱导的大鼠爪水肿模型在体内评估其抗炎活性。 结果：所有化合物在体外显示出中等到良好的NO和iNOS抑制作用。化合物12是NO和iNOS最有效的抑制剂。因此，对其进行了毒性和抗炎活性评估。研究结果发现，它在急性毒性研究中是安全的，并且能够显著减少大鼠爪水肿。其抗炎行为类似于选择性iNOS抑制剂氨基胍。 结论：新合成的苯并咪唑-香豆素杂化物可能成为开发新型抗iNOS剂的潜在前导化合物。
• Design, synthesis and biological evaluation of coumarin alkylamines as potent and selective dual binding site inhibitors of acetylcholinesterase
  作者：Marco Catto、Leonardo Pisani、Francesco Leonetti、Orazio Nicolotti、Paolo Pesce、Angela Stefanachi、Saverio Cellamare、Angelo Carotti

  DOI：10.1016/j.bmc.2012.10.045

  日期：2013.1

  Acetylcholinesterase inhibitors (AChEIs) are currently the drugs of choice, although only symptomatic and palliative, for the treatment of Alzheimer's disease (AD). Donepezil is one of most used AChEIs in AD therapy, acting as a dual binding site, reversible inhibitor of AChE with high selectivity over butyrylcholinesterase (BChE). Through a combined target-and ligand-based approach, a series of coumarin alkylamines matching the structural determinants of donepezil were designed and prepared. 6,7-Dimethoxycoumarin derivatives carrying a protonatable benzylamino group, linked to position 3 by suitable linkers, exhibited fairly good AChE inhibitory activity and a high selectivity over BChE. The inhibitory potency was strongly influenced by the length and shape of the spacer and by the methoxy substituents on the coumarin scaffold. The inhibition mechanism, assessed for the most active compound 13 (IC50 7.6 nM) resulted in a mixed-type, thus confirming its binding at both the catalytic and peripheral binding sites of AChE. (C) 2012 Elsevier Ltd. All rights reserved.
• AHLUWALIA V. K.; BHAT K.; PRAKASH C., HETEROCYCLES, 1979, 12, NO 9, 1205-1206
  作者：AHLUWALIA V. K.、 BHAT K.、 PRAKASH C.

  DOI：——

  日期：——