3-(3-chlorophenyl)-4-hydroxyfuran-2(5H)-one | 100074-42-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(3-chlorophenyl)-4-hydroxyfuran-2(5H)-one
• 英文别名: 4-(3-chlorophenyl)-3-hydroxy-2H-furan-5-one
• CAS: 100074-42-8
• 化学式: C₁₀H₇ClO₃
• 分子量: 210.617
• InChiKey: BXROHWAZZNIVNF-UHFFFAOYSA-N

物化性质

• 沸点：
  433.8±45.0 °C(Predicted)
• 密度：
  1.518±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 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：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-chlorophenyl)-4-hydroxyfuran-2(5H)-one 在 三氯化磷 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(3-chlorophenyl)-4-(propylamino)furan-2(5H)-one
  参考文献：
  名称：

  Synthesis, structure, molecular docking, and structure–activity relationship analysis of enamines: 3-Aryl-4-alkylaminofuran-2(5H)-ones as potential antibacterials

  摘要：

  Thirty-one 3-aryl-4-alkylaminofuran-2(5H)-ones were designed, prepared and tested for their antibacterial activity. Some of them showed significant antibacterial activity against Gram-positive organisms, especially against Staphylococcus aureus ATCC 25923, but all were inactive against Gram-negative organisms. Out of these compounds, 3-(4-bromophenyl)-4-(2-(4-nitrophenyl)hydrazinyl)furan-2(5H)-one (4a11) showed the most potent antibacterial activity against S. aureus ATCC 25923 with MIC50 of 0.42 mu g/mL. The enzyme assay revealed that the possible antibacterial mechanism of the synthetic compounds might be due to their inhibitory activity against tyrosyl-tRNA synthetase. Molecular dockings of 4a11 into S. aureus tyrosyl-tRNA synthetase active site were also performed. This inhibitor snugly fitting the active site might well explain its excellent inhibitory activity. Meanwhile, this modeling disclosed that a more suitable optimization strategy might be to modify the benzene ring at 3-position of furanone with hydrophilic groups. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.051
• 作为产物：
  描述：

  3-氯苯乙酸 在 potassium tert-butylate 、 sodium ethanolate 作用下， 以 乙醇 、 叔丁醇 为溶剂， 反应 5.0h， 生成 3-(3-chlorophenyl)-4-hydroxyfuran-2(5H)-one
  参考文献：
  名称：

  （E）-和（Z）-pulvinones的合成

  摘要：

  已经开发出两种新的途径获得pulvinones，其中一种涉及新颖的Wittig反应。首次报道了E系列的成员，包括母体（E）-普尔维酮，并描述了几何异构体的结构。提出了一种将（E）-普尔维酮定量转化为（Z）-普尔维酮的方法，以及区分异构体的技术。

  DOI：

  10.1039/p19850001567

文献信息

• Synthesis of (E)- and (Z)-pulvinones
  作者：Alexander C. Campbell、Maurice S. Maidment、John H. Pick、Donald F. M. Stevenson

  DOI：10.1039/p19850001567

  日期：——

  one of which involves a novel Wittig reaction. For the first time, members of the E-series, including the parent (E)-pulvinone, are reported and the structural elucidation of the geometric isomers is described. A method for quantitatively converting (E)-pulvinones into (Z)-pulvinones is presented, together with a technique for differentiating between the isomers.

  已经开发出两种新的途径获得pulvinones，其中一种涉及新颖的Wittig反应。首次报道了E系列的成员，包括母体（E）-普尔维酮，并描述了几何异构体的结构。提出了一种将（E）-普尔维酮定量转化为（Z）-普尔维酮的方法，以及区分异构体的技术。
• Synthesis and evaluation of adenosine containing 3-arylfuran-2(5 H )-ones as tyrosyl-tRNA synthetase inhibitors
  作者：Wei Wei、Qi Liu、Zhen-Zhen Li、Wei-Kang Shi、Xing Fu、Jia Liu、Xuan Zhu、Xiao-Cong Wang、Ning Xu、Teng-Fei Li、Fu-Rui Jiang、Zhu-Ping Xiao、Hai-Liang Zhu

  DOI：10.1016/j.ejmech.2017.03.074

  日期：2017.6

  Tyrosyl-tRNA synthetase (TyrRS) is an aminoacyl-tRNA synthetase family protein that possesses an essential role in bacterial protein synthesis. The synthesis, structure-activity relationship, and evolution of a novel series of adenosine-containing 3-arylfuran-2(5H)-ones as TyrRS inhibitors are described. Advanced compound d3 from this series exhibited excellent affinity for TyrRS with IC50 of 0.61

  酪氨酰-tRNA合成酶（TyrRS）是一种氨酰基-tRNA合成酶家族蛋白，在细菌蛋白合成中具有重要作用。描述了一系列新型的含腺苷的3-芳基呋喃-2（5H）-酮作为TyrRS抑制剂的合成，结构-活性关系和演变。该系列的先进化合物d3对TyrRS表现出优异的亲和力，IC50为0.61±0.04μM。细菌生长抑制试验表明，d3对大肠杆菌和铜绿假单胞菌显示出亚微摩尔抗菌力，并且与市售的环丙沙星抗生素相比。
• 4-Alkoxy-3-arylfuran-2(5H)-ones as inhibitors of tyrosyl-tRNA synthetase: Synthesis, molecular docking and antibacterial evaluation
  作者：Zhu-Ping Xiao、Hui Ouyang、Xu-Dong Wang、Peng-Cheng Lv、Ze-Jun Huang、She-Rong Yu、Tian-Fang Yi、Ye-Ling Yang、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2011.05.042

  日期：2011.7

  A series of novel 4-alkoxy-3-arylfuran-2(5H)-ones as tyrosyl-tRNA synthetase inhibitors were synthesized. Of these compounds, 3-(4-hydroxyphenyl)-4-(2-morpholinoethoxy)furan-2(5H)-one (27) was the most potent. The binding model and structure-activity relationship indicate that replacement of morpholine-ring in the side chain of 27 with a substituent containing more hydrophilic groups would be more suitable for further modification. Antibacterial assay revealed that the synthetic compounds are effective against growth of Gram-positive organisms, and 27 is the most potent agent against Staphylococcus ;aureus ATCC 25923 with MIC50 value of 0.23 mu g/mL. (C) 2011 Elsevier Ltd. All rights reserved.
• Tyrosyl-tRNA synthetase inhibitors as antibacterial agents: Synthesis, molecular docking and structure–activity relationship analysis of 3-aryl-4-arylaminofuran-2(5H)-ones
  作者：Zhu-Ping Xiao、Tao-Wu Ma、Mei-Lin Liao、Yu-Ting Feng、Xiao-Chun Peng、Jia-Liang Li、Zhi-Ping Li、Ying Wu、Qun Luo、Yang Deng、Xiao Liang、Hai-Liang Zhu

  DOI：10.1016/j.ejmech.2011.07.047

  日期：2011.10

  Thirty-five 3-aryl-4-arylaminofuran-2(5H)-one derivatives were designed, prepared and tested for their inhibitory activity against tyrosyl-tRNA synthetase. Out of these compounds, 3-(3-bromophenyl)-4-(3,5-dichlorophenylamino)furan-2(5H)-one (35) was the most active with IC50 of 0.09 +/- 0.02 mu M. The structure activity relationship revealed that introduction of chlorine atoms at both meta positions of aniline moiety significantly increased the enzyme inhibitory activity. The results of antibacterial assay revealed that the tested compounds showed good activity against Gram-positive bacteria, with 35 being the most potent with MIC50 of 0.06 mu g/mL against Staphylococcus aureus ATCC 25923. Molecular docking of 35 into S. aureus tyrosyl-tRNA synthetase active site was also performed. The inhibitor snugly fitting the active site may well explain its excellent inhibitory activity. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Novel 3-arylfuran-2(5H)-one-fluoroquinolone hybrid: Design, synthesis and evaluation as antibacterial agent
  作者：Xu-Dong Wang、Wei Wei、Peng-Fei Wang、Yun-Tao Tang、Rui-Cheng Deng、Biao Li、Sha-Sha Zhou、Jing-Wen Zhang、Lei Zhang、Zhu-Ping Xiao、Hui Ouyang、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2014.05.018

  日期：2014.7

  3-Arylfuran-2(5H)-one, a novel antibacterial pharmacophore targeting tyrosyl-tRNA synthetase (TyrRS), was hybridized with the clinically used fluoroquinolones to give a series of novel multi-target antimicrobial agents. Thus, twenty seven 3-arylfuran-2(5H)-one-fluoroquinolone hybrids were synthesized and evaluated for their antimicrobial activities. Some of the hybrids exhibited merits from both parents, displaying a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria. The most potent compound (11) in antibacterial assay shows MIC50 of 0.11μg/mL against Multiple drug resistant Escherichia coli, being about 51-fold more potent than ciprofloxacin. The enzyme assays reveal that 11 is a potent multi-target inhibitor with IC50 of 1.15±0.07μM against DNA gyrase and 0.12±0.04μM against TyrRS, respectively. Its excellent inhibitory activities against isolated enzymes and intact cells strongly suggest that 11 deserves to further research as a novel antibiotic.