ethyl 4-oxo-4,5,6,7-tetrahydrobenzo[b]furan-5-yl acetate | 749910-02-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: ethyl 4-oxo-4,5,6,7-tetrahydrobenzo[b]furan-5-yl acetate
• 英文别名: ethyl (4-oxo-4,5,6,7-tetrahydro-1-benzofuran-5-yl)acetate；ethyl 2-(4-oxo-6,7-dihydro-5H-1-benzofuran-5-yl)acetate
• CAS: 749910-02-9
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: LVLXGJILNIGJAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-oxo-4,5,6,7-tetrahydrobenzo[b]furan-5-yl acetate 在 sodium hydroxide 、 1-羟基苯并三唑 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 98.0h， 生成
  参考文献：
  名称：

  New Serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C Receptor Antagonists:  Synthesis, Pharmacology, 3D-QSAR, and Molecular Modeling of (Aminoalkyl)benzo and Heterocycloalkanones

  摘要：

  A series of 52 conformationally constrained butyrophenones have been synthesized and pharmacologically tested as antagonists at 5-HT2A, 5-HT2B, and 5-HT2C serotonin receptors, useful for dissecting the role of each 5-HT2 subtype in pathophysiology. These compounds were also a consistent set for the identification of structural features relevant to receptor recognition and subtype discrimination. Six compounds were found highly active (pK(1) > 8.76) and selective at the 5-HT2A receptor vs 5-HT2B and/or 5-HT2C receptors. Piperidine fragments confer high affinity at the 5-HT2A receptor subtype, with benzofuranone- and thiotetralonepiperidine as the most selective derivatives over 5-HT2C and 5-HT2B receptors, respectively; K-1 2A/2C and/or K-B 2A/2B ratios greater than 100 were obtained. Compounds showing a more pronounced selectivity at 5-HT2A/5-HT2C than at 5-HT2A/5-HT2B bear 6-fluorobenzisoxazolyl- and p-fluorobenzoylpiperidine moieties containing one methylene bridging the basic piperidine, to the alkanone moiety. An ethylene bridge between the alkanone and the amino moieties led to ligands with higher affinities for the 5-HT2B receptor. Significant selectivity at the 5-HT2B receptor vs 5-HT2C was observed with 1-1[(1-oxo-1,2,3,4-tetrahydro-3-naphthyl)methyl-4-[3-(p-fluorobenzoyl)propyl]piperazine (more than 100-fold higher). Although piperidine fragments also confer higher affinity at 5-HT2C receptors, only piperazine-containing ligands were selective over 5-HT2A. Moderate selectivity was observed at 5-HT2C vs 5-HT2B (10-fold) with some compounds bearing a 4-[3-(6-fluorobenzisoxazolyl)]piperidine moiety in its structure. Molecular determinants for antagonists acting at 5-HT2A receptors were identified by 3D-QSAR (GRID-GOLPE) studies. Docking simulations at 5-HT2A and 5-HT2C receptors suggest a binding site for the studied type of antagonists (between transmembrane helices 2, 3, and 7) different to that of the natural agonist serotonin (between 3, 5, and 6).

  DOI：

  10.1021/jm011014y
• 作为产物：
  描述：

  1,3-环己二酮 在 碳酸氢钠 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 34.5h， 生成 ethyl 4-oxo-4,5,6,7-tetrahydrobenzo[b]furan-5-yl acetate
  参考文献：
  名称：

  呋喃 [2,3-h]- 和哒嗪并 [3,4-f]cinnolin-3-ol 支架作为开发新型 HIV-1 整合酶抑制剂的底物的研究

  摘要：

  为了开发新型 HIV-1 整合酶抑制剂，我们获得了一组基于呋喃 [2,3-h]cinnolin-3(2H)-one 和哒嗪基 [3,4-f]cinnolin-的稠环系统。带有潜在螯合药效团的 3-ol 支架，可参与酶的抑制机制。在此，我们报告了这些杂芳族系统的设计、合成、结构研究和初步生物学结果。

  DOI：

  10.3998/ark.5550190.0012.901

文献信息

• Investigation of furo[2,3-h]- and pyridazino[3,4-f]cinnolin-3-ol scaffolds as substrates for the development of novel HIV-1 integrase inhibitors
  作者：Mohamed F. Y. Gomaa、Nicolino Pala、Marco Derudas、Jehan Abd-Elrazik Hasanen、El-Sayed H. El-Tamany、Paola Casule、Alberto Mariani、Mario Sechi

  DOI：10.3998/ark.5550190.0012.901

  日期：——

  With the aim to develop novel HIV-1 integrase inhibitors, we obtained a set of condensed ring systems based on the furo[2,3-h]cinnolin-3(2H)-one and pyridazino[3,4-f]cinnolin-3-ol scaffolds bearing a potential chelating pharmacophore, which can be involved in the inhibition mechanism of the enzyme. Herein, we report the design, synthesis, structural investigation and preliminary biological results

  为了开发新型 HIV-1 整合酶抑制剂，我们获得了一组基于呋喃 [2,3-h]cinnolin-3(2H)-one 和哒嗪基 [3,4-f]cinnolin-的稠环系统。带有潜在螯合药效团的 3-ol 支架，可参与酶的抑制机制。在此，我们报告了这些杂芳族系统的设计、合成、结构研究和初步生物学结果。
• New Serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C Receptor Antagonists:  Synthesis, Pharmacology, 3D-QSAR, and Molecular Modeling of (Aminoalkyl)benzo and Heterocycloalkanones
  作者：José Brea、Jordi Rodrigo、Antonio Carrieri、Ferran Sanz、M. Isabel Cadavid、María J. Enguix、María Villazón、Guadalupe Mengod、Yolanda Caro、Christian F. Masaguer、Enrique Raviña、Nuria B. Centeno、Angelo Carotti、M. Isabel Loza

  DOI：10.1021/jm011014y

  日期：2002.1.1

  A series of 52 conformationally constrained butyrophenones have been synthesized and pharmacologically tested as antagonists at 5-HT2A, 5-HT2B, and 5-HT2C serotonin receptors, useful for dissecting the role of each 5-HT2 subtype in pathophysiology. These compounds were also a consistent set for the identification of structural features relevant to receptor recognition and subtype discrimination. Six compounds were found highly active (pK(1) > 8.76) and selective at the 5-HT2A receptor vs 5-HT2B and/or 5-HT2C receptors. Piperidine fragments confer high affinity at the 5-HT2A receptor subtype, with benzofuranone- and thiotetralonepiperidine as the most selective derivatives over 5-HT2C and 5-HT2B receptors, respectively; K-1 2A/2C and/or K-B 2A/2B ratios greater than 100 were obtained. Compounds showing a more pronounced selectivity at 5-HT2A/5-HT2C than at 5-HT2A/5-HT2B bear 6-fluorobenzisoxazolyl- and p-fluorobenzoylpiperidine moieties containing one methylene bridging the basic piperidine, to the alkanone moiety. An ethylene bridge between the alkanone and the amino moieties led to ligands with higher affinities for the 5-HT2B receptor. Significant selectivity at the 5-HT2B receptor vs 5-HT2C was observed with 1-1[(1-oxo-1,2,3,4-tetrahydro-3-naphthyl)methyl-4-[3-(p-fluorobenzoyl)propyl]piperazine (more than 100-fold higher). Although piperidine fragments also confer higher affinity at 5-HT2C receptors, only piperazine-containing ligands were selective over 5-HT2A. Moderate selectivity was observed at 5-HT2C vs 5-HT2B (10-fold) with some compounds bearing a 4-[3-(6-fluorobenzisoxazolyl)]piperidine moiety in its structure. Molecular determinants for antagonists acting at 5-HT2A receptors were identified by 3D-QSAR (GRID-GOLPE) studies. Docking simulations at 5-HT2A and 5-HT2C receptors suggest a binding site for the studied type of antagonists (between transmembrane helices 2, 3, and 7) different to that of the natural agonist serotonin (between 3, 5, and 6).