4-methyldihydrofuro[2,3-h]coumarin-9-one | 93353-47-0

• 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: 4-methyldihydrofuro[2,3-h]coumarin-9-one
• 英文别名: 4-Methyl-2H-furo[2,3-H]chromene-2,9(8H)-dione；4-methylfuro[2,3-h]chromene-2,9-dione
• CAS: 93353-47-0
• 化学式: C₁₂H₈O₄
• mdl: MFCD01816730
• 分子量: 216.193
• InChiKey: DPEBIOMWFKNMDW-UHFFFAOYSA-N

物化性质

• 沸点：
  452.3±45.0 °C(Predicted)
• 密度：
  1.424±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-methyldihydrofuro[2,3-h]coumarin-9-one 在 对甲苯磺酸 、 magnesium chloride 作用下， 以 二氯甲烷 为溶剂， 反应 11.0h， 生成 8-methyl-1-methoxycarbonyl-4-((pyrrolidin-1-yl)carbonyl)pyridazino[4,5-j]angelicin
  参考文献：
  名称：

  Synthesis and convenient functionalisation of pyridazinofurocoumarins: nitrogenated isosters of potent DNA inhibitors

  摘要：

  Pyridazino[3,4-h]psoralens and pyridazino[3,4-j]angelicins are prepared in good yield from resorcinols through a direct, easy and generally applicable synthetic route. The key step in this route is the inverse electron-demand Diels-Alder reaction between linear or angular furocoumarins and 3,6-bis(methoxycarbonyl)-1,2,4,5-tetrazine to give the dicarboxymethylated tetracycles. The ester group in the peri position with respect to the oxygen in the furan ring can be regioselectively transformed to give primary or secondary amides. Similarly, the two ester groups in the tetracycle can be transformed in a high-efficiency process to give bis-amides that can be either symmetrical (from the same amine) or unsymmetrical (from two different amines). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.08.051
• 作为产物：
  描述：

  4-甲基-2-氧代-2H-色烯-7-基 氯乙酸酯 在 aluminum (III) chloride 作用下， 反应 0.5h， 生成 4-methyldihydrofuro[2,3-h]coumarin-9-one
  参考文献：
  名称：

  一种苯并香豆素查尔酮类神经氨酸酶抑制剂 及其制备方法和应用

  摘要：

  本发明涉及生物医药技术领域，具体涉及一种苯并香豆素查尔酮类神经氨酸酶抑制剂及其制备方法和应用，该抑制剂，其具有式I所示的结构：本发明中的化合物结构新颖，实验表明具有良好的神经氨酸酶抑制活性，有望用于制备抑制神经氨酸酶活性的药物。

  公开号：

  CN111533754B

文献信息

• Design, synthesis and biological evaluation of dihydrofurocoumarin derivatives as potent neuraminidase inhibitors
  作者：Zhi Jian Zhong、Li Ping Cheng、Wan Pang、Xue Song Zheng、Shi Kai Fu

  DOI：10.1016/j.bmcl.2021.127839

  日期：2021.4

  Neuraminidase (NA) is a promising target for development of anti-influenza drugs. In this study a dihydrofurocoumarin derivative ZINC05577497 was discovered as a lead NA inhibitor based on docking-based virtual screening technique. The optimization of lead ZINC05577497 led to the discovery of a series of novel NA inhibitors 5a-5j. Compound 5b has the most potent activity against NA with IC50 = 0.02 µM

  神经氨酸酶（NA）是开发抗流感药物的有希望的靶点。在这项研究中，基于基于对接的虚拟筛选技术，发现了一种二氢呋喃香豆素衍生物ZINC05577497作为 NA 的先导抑制剂。铅ZINC05577497的优化导致了一系列新型NA抑制剂5a - 5j的发现。化合物5b对 NA 的活性最强，IC 50  = 0.02 µM，低于参考羧酸奥司他韦 (OSC) (IC 50  = 0.04 µM) 和ZINC05577497 (IC 50 = 0.11 µM）。其他目标化合物也显示出对 NA 活性的潜在抑制作用。分子对接结果表明，5b的良好效力可能归因于二氢呋喃香豆素环延伸至 150 个空腔。本文的结果将有助于发现更有效的 NA 抑制剂。
• 对位取代的二氢呋喃香豆素类神经氨酸酶抑制剂及其制备方法和应用
  申请人：上海应用技术大学

  公开号：CN111925377B

  公开（公告）日：2022-05-31

  本发明涉及生物医药技术领域，具体涉及一种对位取代的二氢呋喃香豆素类神经氨酸酶抑制剂及其制备方法和应用，该抑制剂，其具有式I所示的结构：本发明中的化合物结构新颖，实验表明具有良好的神经氨酸酶抑制活性，有望用于制备抑制神经氨酸酶活性的药物。
• Kravchenko; Chibisova; Traven', Russian Journal of Organic Chemistry, 1999, vol. 35, # 6, p. 899 - 909
  作者：Kravchenko、Chibisova、Traven'

  DOI：——

  日期：——
• ——
  作者：O. B. Safonova、D. V. Kravchenko、I. N. Senchenya、V. F.Traven'

  DOI：10.1023/a:1012331118017

  日期：——

  Tautomeric transformations of 4-methyldihydrofuro[2,3-h]coumarin-9-one and its 8-substituted derivatives were studied by H-1 NMR, electronic absorption spectroscopy, and quantum chemistry. The 1H NMR spectra of these compounds in CDCl3 show that they exist in the ketone form, and in more polar solvents they can pass into the enol form. By electronic absorption spectroscopy it was established that the derivatives containing electron-acceptor substituents in the 8 position of the furanone ring undergo tautomeric transformations as the composition of the solvent is varied from 100% methanol to 100% CCl4. At the same time, the derivatives with electron-donor substituents in the same position do not show any specific alterations in the absorption spectra with solvent. Analogous pattern was observed in the enolization Or Substituted dihydrofurocoumarinones by acetylation: In presence of electron-donor substituents in the 8 position, no acetylation occurred, while with the compounds containing electron-acceptor substituents, the corresponding 9-acetoxy-4-methylangelicins were prepared in high yields. Calculations by the PPP/CI method of the electronic absorption spectra 4-methyldihydrofuro[2,3-h]coumarin-9-one showed that in polar solvents (methanol) it prefers the enol form. Data of spectral measurements were compared with results of semiempirical (MNDO, AM1, and PM3) and nonempirical quantum-chemical calculations (with 3-21G, 6-31G*, and 31G** basis sets).