3-Esanoyl-4-hydroxy-6-methyl-2H-pyran-2-on | 27424-82-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-Esanoyl-4-hydroxy-6-methyl-2H-pyran-2-on
• 英文别名: 2H-Pyran-2-one, 4-hydroxy-6-methyl-3-(1-oxohexyl)-；3-hexanoyl-4-hydroxy-6-methylpyran-2-one
• CAS: 27424-82-4
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: ADCLDRLWUWHAKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-Esanoyl-4-hydroxy-6-methyl-2H-pyran-2-on 在 盐酸 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 水 为溶剂， 以76%的产率得到3-hexyl-4-hydroxy-6-methyl-2-pyrone
  参考文献：
  名称：

  Efficacy of a series of alpha-pyrone derivatives against Leishmania (L.) infantum and Trypanosoma cruzi

  摘要：

  The neglected tropical diseases Chagas disease and leishmaniasis affect together more than 20 million people living mainly in developing countries. The mainstay of treatment is chemotherapy, however the drugs of choice, which include benznidazole and miltefosine, are toxic and have numerous side effects. Safe and effective therapies are urgently needed. Marine alpha-pyrones have been previously identified as scaffolds with potential antiprotozoan activities. In this work, using a phenotypic screen, twentyseven examples of 3-substituted 4-hydroxy-6-methyl alpha-pyrones were synthesized and their anti parasitic efficacy evaluated against Leishmania (L.) infantum and Trypanosoma cruzi in order to evaluate structure-activity relationships within the series. The mechanism of action and the in vivo efficacy of the most selective compound against T cruzi were evaluated using different techniques. In vitro data indicated that compounds 8, 15, 25, 26 and 28 presented IC50 values in the range between 13 and 54 mu M against L infantum intracellular amastigotes. Among them, hexanoyl substituted pyrone 8 was the most selective and potent, with a Selectivity Index (SI) > 14. Fifteen of the alpha-pyrones were effective against T cruzi trypomastigotes, with 3-undecanoyl (11) and 3-tetradecanoyl (12) substituted pyrones being the most potent against trypomastigotes, with IC50 values of 1 and 2 mu M, respectively, and SI higher than 70. Using flow cytometry and fluorescent-based assays, pyrone 12 was found to induce hyperpolarization of the mitochondrial membrane potential of T. cruzi, without affecting plasma membrane permeability. An experimental acute phase-murine model, demonstrated that in vivo dosing of 12 (30 mg/kg/day; 5 days), had no efficacy at the first parasitemia onset of T. cruzi, but reduced the second onset by 55% (p < 0.05), suggesting a delayed action in BALB/c mice. Additionally, a histopathology study demonstrated no toxic effects to the treated mice. The finding that several 3-substituted alpha-pyrones have in vitro efficacy against both L. infantum and T. cruzi, and that one analogue exhibited moderate and non-toxic in vivo efficacy against T. cruzi is encouraging, and suggests that this compound class should be explored as longterm treatments in experimental Chagas disease. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.08.055
• 作为产物：
  描述：

  4-羟基-6-甲基-2-吡喃酮 、 己酰氯 在 三氟乙酸 作用下， 生成 3-Esanoyl-4-hydroxy-6-methyl-2H-pyran-2-on
  参考文献：
  名称：

  取代了2-吡喃酮，2-吡啶酮和其他弹性蛋白，作为治疗慢性阻塞性肺疾病的潜在药物。

  摘要：

  已经合成了几种弹性蛋白（I）的同源物，并显示出它们抑制人白细胞弹性蛋白酶（HLE）。发现C-3烷基取代的2-吡喃酮11和12是该酶的最有效抑制剂。这些化合物在抑制活性方面具有高度特异性。

  DOI：

  10.1021/jm00146a023

文献信息

• Substituted 2-pyrones, 2-pyridones, and other congeners of elasnin as potential agents for the treatment of chronic obstructive lung diseases
  作者：William C. Groutas、Michael A. Stanga、Michael J. Brubaker、Tien L. Huang、Min K. Moi、Robert T. Carroll

  DOI：10.1021/jm00146a023

  日期：1985.8

  Several congeners of elasnin (I) have been synthesized and shown to inhibit human leukocyte elastase (HLE). The C-3 alkyl substituted 2-pyrones 11 and 12 were found to be the most effective inhibitors of the enzyme. These compounds are highly specific in their inhibitory activity.

  已经合成了几种弹性蛋白（I）的同源物，并显示出它们抑制人白细胞弹性蛋白酶（HLE）。发现C-3烷基取代的2-吡喃酮11和12是该酶的最有效抑制剂。这些化合物在抑制活性方面具有高度特异性。
• Chelation of the Optimal Antifungal Pogostone Analogue with Copper(II) to Explore the Dual Antifungal and Antibacterial Agent
  作者：Delong Wang、Chunxia Yuan、Yunpeng Li、Shuhong Bai、Juntao Feng、Yong Wang、Yali Fang、Zhijia Zhang

  DOI：10.1021/acs.jafc.3c07050

  日期：2024.2.28

  The 3D-QSAR models generated using Topomer comparative molecular field analysis indicated that a shorter alkyl chain (carbon atom number <8), terminal rings, or electron-deficient groups on the alkyl side chain are beneficial for antifungal potency. Further, bioassay results revealed that the component of 21 in complex 34 dominated the antifungal activity, but the introduction of Cu(II) significantly

  在不断探索更有效的抗真菌 pogostone (Po) 类似物的过程中，我们保留了先前确定的 3-乙酰基-4-羟基-2-吡喃酮核心基序，同时合成了一系列烷基侧链发生变化的 Po 类似物。体外生物测定结果表明，化合物21是最有效的抗真菌类似物，对核盘菌( Sclerotinia sclerotiorum (Lib.) de Bary)的EC 50值为1.1 μg/mL。同时，其Cu(II)络合物34对野油菜黄单胞菌( Xanthomonascampestris pvcampestris )( Xcc )的抗菌活性较21 (MIC=700μg/mL)显着增强，最低抑菌浓度(MIC)为300μg/mL。复合物34对油菜叶片中的核盘菌和Xcc具有显着的预防效果，防效分别为98.8%（50 μg/mL）和80.7%（1000 μg/mL）。使用Topomer比较分子场分析生成的3D-QSAR模型表明
• Inhibition of human sputum elastase by substituted 2-pyrones. 2
  作者：Luisa Cook、Bela Ternai、Peter Ghosh

  DOI：10.1021/jm00389a010

  日期：1987.6

  Nineteen 4-hydroxy- and 4-methoxy-2-pyrones related to elasnin (I) have been assayed for in vitro inhibition of human sputum elastase (HSE), porcine pancreatic elastase, alpha-chymotrypsin, and trypsin. Inhibition is reported as Ki and Ki'; percentage inhibition was dependent on [S] in a number of cases, making it unsuitable as a measure of relative inhibition. The 3-(1-oxoalkyl)-4-hydroxy-6-alkyl-2-pyrones were found to be most effective, the octyl homologue 11 being the most potent inhibitor (Ki = 4.6 microM, 30 times better than the lead compound). A further reduction in inhibition was observed when the hitherto hydrophobic 6-substituent was substituted by a branched functionality of hydrophilic nature. Conversely, methylation of the 4-hydroxy group of the 6-alkyl-2-pyrones increased inhibitory activity. The mechanism of inhibition varied from pure noncompetitive to mixed type to uncompetitive and was found to be dependent on the pattern of substitution. We believe that the 4-hydroxy-2-pyrone binds to the S4 subsite, with the 6-substituent extending across the S4-S1 subsites and the 3-substituent occupying the S5 subsite. The length of the inhibitor binding region was calculated to be approximately 24 A. None of the hydrophobic compounds were found to have any appreciable inhibition (less than 10%) with porcine pancreatic elastase, bovine alpha-chymotrypsin, and bovine trypsin when tested at the limit of their solubility. The hydrophilic compounds were nonspecific, inhibiting all four enzymes. Dialysis was used to show that the interaction is fully reversible.
• EP0365539A4
  申请人：——

  公开号：EP0365539A4

  公开（公告）日：1990-12-05
• HUMAN LEUCOCYTE ELASTASE INHIBITOR COMPOUNDS
  申请人：AUSTRALIAN COMMERCIAL RESEARCH & DEVELOPMENT LIMITED

  公开号：EP0365539A1

  公开（公告）日：1990-05-02