(2Z)-2-(4-fluorobenzylidene)-4,6-dimethoxy-1-benzofuran-3(2H)-one | 350982-87-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 橙酮类黄酮
• 英文名称: (2Z)-2-(4-fluorobenzylidene)-4,6-dimethoxy-1-benzofuran-3(2H)-one
• 英文别名: (Z)-2-(4-fluorobenzylidene)-4,6-dimethoxybenzofuran-3(2H)-one；(Z)-4,6-dimethoxy-(4'-fluorobenzylidene)benzofuran-3(2H)-one；4,6-dimethoxy-2-(4'-fluorobenzylidene)benzofuran-3(2H)-one；(2Z)-2-[(4-fluorophenyl)methylidene]-4,6-dimethoxy-1-benzofuran-3-one
• CAS: 350982-87-5
• 化学式: C₁₇H₁₃FO₄
• 分子量: 300.286
• InChiKey: DEFCYYCAIYFANA-CHHVJCJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2Z)-2-(4-fluorobenzylidene)-4,6-dimethoxy-1-benzofuran-3(2H)-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以50%的产率得到2-(4-fluorobenzylidene)-4,6-dihydroxybenzofuran-3(2H)-one
  参考文献：
  名称：

  Discovery of Naturally Occurring Aurones That Are Potent Allosteric Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase

  摘要：

  We have identified naturally occurring 2-benzylidenebenzofuran-3-ones (aurones) as new templates for non-nucleoside hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors. The aurone target site, identified by site-directed mutagenesis, is located in thumb pocket I of HCV RdRp. The RdRp inhibitory activity of 42 aurones was rationally explored in an enzyme assay. Molecular docking studies were used to determine how aurones bind to HCV RdRp and to predict their range of inhibitory activity. Seven aurone derivatives were found to have potent inhibitory effects on HCV RdRp, with IC(50) below 5 mu M and excellent selectivity index (inhibition activity versus cellular cytotoxicity). The most active aurone analogue was (Z)-2-((1-butyl-1H-indo1-3-yl)methylene)-4,6-dihydroxybenzofuran-3(2H)-one (compound 51), with an IC(50) of 2.2 mu M. Their potent RdRp inhibitory activity and their low toxicity make these molecules attractive candidates as direct-acting anti-HCV agents.

  DOI：

  10.1021/jm200242p
• 作为产物：
  描述：

  2-hydroxy-4,6-dimethoxy-4'-fluorochalcone 在 双氧水 作用下， 以 水 为溶剂， 反应 24.0h， 以189 mg的产率得到(2Z)-2-(4-fluorobenzylidene)-4,6-dimethoxy-1-benzofuran-3(2H)-one
  参考文献：
  名称：

  A One-Pot Synthesis of Aurones from Substituted Acetophenones and Benz­aldehydes: A Concise Synthesis of Aureusidin

  摘要：

  A one-pot synthesis of aurones from substituted acetophenone and benzaldehyde has been developed on the basis of an improved Algar-Flynn-Oyamada reaction. By using this method, several aurones were prepared in three steps from commercial starting materials. The usefulness of this one-pot strategy was confirmed by a synthesis of aureusidin, an inhibitor of iodothyronine deiodinase, in 41% overall yield. In comparison with a two-step synthesis of this product from the same substrates, the one-pot strategy was more effective, giving a higher yield and requiring fewer and simpler operations.

  DOI：

  10.1055/s-0031-1291153

文献信息

• 4-Hydroxy-6-methoxyaurones with High-Affinity Binding to Cytosolic Domain of P-Glycoprotein.
  作者：Ahcène Boumendjel、Chantal Beney、Nabajyoti Deka、Anne-Marie Mariotte、Martin Ata Lawson、Doriane Trompier、Hélène Baubichon-Cortay、Attilio Di Pietro

  DOI：10.1248/cpb.50.854

  日期：——

  A series of 4-hydroxy-6-methoxyaurones and 4,6-dimethoxyaurones has been synthesised and tested for their binding affinity toward the nucleotide-binding domain of P-glycoprotein, an ABC (ATP-Binding Cassette) transporter which mediates the resistance of cancer cells to chemotherapy. These compounds differ from each other by the nature of the substituent on the aurone B-ring. The binding affinity seems to be linked to the nature of the substituent, as well as to the presence or the absence of a hydroxy group at position 4. The most active compounds were 4′-bromo-4-hydroxy-6-methoxyaurone and 4-hydroxy-4′-iodo-6-methoxyaurone.

  一系列的4-羟基-6-甲氧基黄烷酮和4,6-二甲氧基黄烷酮已经被合成并测试了其对P-糖蛋白核苷酸结合域的结合亲和力，P-糖蛋白是一种介导癌细胞耐药性对化疗的ABC（ATP结合盒）转运蛋白。这些化合物在黄烷酮B环上的取代基性质上有差异。结合亲和力似乎与取代基的性质以及4位上羟基的有无相关。活性最强的化合物是4′-溴-4-羟基-6-甲氧基黄烷酮和4-羟基-4′-碘-6-甲氧基黄烷酮。
• 1-Azaaurones derived from the naturally occurring aurones as potential antimalarial drugs
  作者：Florence Souard、Sabrina Okombi、Chantal Beney、Séverine Chevalley、Alexis Valentin、Ahcène Boumendjel

  DOI：10.1016/j.bmc.2010.06.008

  日期：2010.8

  We report the synthesis and in vitro antiplasmodial activity of 35 compounds, designed as analogues of the naturally occurring aurones. Several of these analogues showed submicromolar antimalarial activity against a chloroquine-resistant strain of Plasmodium falciparum (FcB1-Columbia strain) cultured on human erythrocytes. Substitution of the intracyclic oxygen in aurones by a nitrogen atom and systematic

  我们报告了35种化合物的合成和体外抗疟原虫活性，这些化合物被设计为天然存在的金刚烷的类似物。这些类似物中的几种显示出对在人红细胞上培养的恶性疟原虫抗氯喹菌株（FcB1-Columbia菌株）的亚微摩尔抗疟活性。氮原子将金环素中的环内氧取代，并且B环上取代基的系统变化表明，有前途的铅对CQ耐药菌株表现出良好的活性。特别地，4，6-二甲氧基-4'-乙基氮杂金酮22显示出抗疟原虫效力而没有明显的毒性。该化合物家族的容易合成和相关的抗疟原虫活性有利于有希望的进一步发展的候选物。
• Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR
  作者：Chong-Yew Lee、Eng-Hui Chew、Mei-Lin Go

  DOI：10.1016/j.ejmech.2010.03.023

  日期：2010.7

  The chemopreventive potential of functionalized aurones and related compounds as inducers of NAD(P) H:quinone oxidoreductase 1 (NQO1, EC 1.6.99.2) are described. Several 4,6-dimethoxy and 5-hydroxyaurones induced NQO1 activity of Hepa1c1c7 cells by 2-fold at submicromolar concentrations, making these the most potent inducers to be identified from this class. Mechanistically, induction of NQO1 was mediated by the activation of AhR/XRE and Nrf2/ARE pathways, indicating that aurones may be mixed activators of NQO1 induction or agents capable of exploiting the proposed cross-talk between the AhR and Nrf2 gene batteries. QSAR analysis by partial least squares projection to latent structures (PLS) identified size parameters, in particular those associated with non-polar surface areas, as an important determinant of induction activity. These were largely determined by the substitution on rings A and B. A stereoelectronic role for the exocyclic double bond as reflected in the E-LUMO term was also identified. The electrophilicity of the double bond or its effect on the conformation of the target compound are possible key features for induction activity. (c) 2010 Elsevier Masson SAS. All rights reserved.
• An Efficient Synthesis of 4,6-Dimethoxyaurones
  作者：Ahcène Boumendjel、Chantal Beney、Anne-Marie Mariotte

  DOI：10.3987/com-01-9182

  日期：——
• Discovery of Naturally Occurring Aurones That Are Potent Allosteric Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase
  作者：Romain Haudecoeur、Abdelhakim Ahmed-Belkacem、Wei Yi、Antoine Fortuné、Rozenn Brillet、Catherine Belle、Edwige Nicolle、Coralie Pallier、Jean-Michel Pawlotsky、Ahcène Boumendjel

  DOI：10.1021/jm200242p

  日期：2011.8.11

  We have identified naturally occurring 2-benzylidenebenzofuran-3-ones (aurones) as new templates for non-nucleoside hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors. The aurone target site, identified by site-directed mutagenesis, is located in thumb pocket I of HCV RdRp. The RdRp inhibitory activity of 42 aurones was rationally explored in an enzyme assay. Molecular docking studies were used to determine how aurones bind to HCV RdRp and to predict their range of inhibitory activity. Seven aurone derivatives were found to have potent inhibitory effects on HCV RdRp, with IC(50) below 5 mu M and excellent selectivity index (inhibition activity versus cellular cytotoxicity). The most active aurone analogue was (Z)-2-((1-butyl-1H-indo1-3-yl)methylene)-4,6-dihydroxybenzofuran-3(2H)-one (compound 51), with an IC(50) of 2.2 mu M. Their potent RdRp inhibitory activity and their low toxicity make these molecules attractive candidates as direct-acting anti-HCV agents.