3,3-bis-(3-fluoro-4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: 3,3-bis-(3-fluoro-4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one
• 英文别名: 3,3-Bis(3-fluoro-4-hydroxy-phenyl)benzo[g]isobenzofuran-1-one；3,3-bis(3-fluoro-4-hydroxyphenyl)benzo[g][2]benzofuran-1-one
• 化学式: C₂₄H₁₄F₂O₄
• 分子量: 404.37
• InChiKey: MZAQKJGJNGPFRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,2-萘二酸酐 、 2-氟苯酚 在 硫酸 作用下， 反应 5.0h， 以6.8%的产率得到3,3-bis-(3-fluoro-4-hydroxyphenyl)-1H-naphtho[1,2-c]furan-3-one
  参考文献：
  名称：

  Antibacterial Agent Discovery Using Thymidylate Synthase Biolibrary Screening

  摘要：

  Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate to 2'-deoxythymidine 5'-monophosphate, an essential precursor for DNA synthesis. A specific inhibition of this enzyme induces bacterial cell death. As a second round lead optimization design, new 1,2-naphthalein derivatives have been synthesized and tested against a TS-based biolibrary, including human thymidylate synthase (hTS). Docking studies have been performed to rationalize the experimentally observed affinity profiles of 1,2-naphthalein compounds toward Lactobacillus casei TS and hTS. The best TS inhibitors have been tested against a number of clinical isolates of Gram-positive-resistant bacterial strains. Compound 3,3-bis(3,5-dibromo-4-hydroxyphenyl)-1H, 3H-naphtho[1,2-c]furan-1-one(5) showed significant antibacterial activity, no in vitro toxicity, and dose-response effects against Staphylococcus epidermidis (MIC = 0.5-2.5 mu g/mL) clinical isolate strains, which are resistant to at least 17 of the best known antibacterial agents, including vancomycin. So far this compound can be regarded as a leading antibacterial agent.

  DOI：

  10.1021/jm051187d

文献信息

• Antibacterial Agent Discovery Using Thymidylate Synthase Biolibrary Screening
  作者：M. Paola Costi、Arianna Gelain、Daniela Barlocco、Stefano Ghelli、Fabrizia Soragni、Fabiano Reniero、Tiziana Rossi、Antonio Ruberto、Claude Guillou、Antonio Cavazzuti、Chiara Casolari、Stefania Ferrari

  DOI：10.1021/jm051187d

  日期：2006.10.1

  Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate to 2'-deoxythymidine 5'-monophosphate, an essential precursor for DNA synthesis. A specific inhibition of this enzyme induces bacterial cell death. As a second round lead optimization design, new 1,2-naphthalein derivatives have been synthesized and tested against a TS-based biolibrary, including human thymidylate synthase (hTS). Docking studies have been performed to rationalize the experimentally observed affinity profiles of 1,2-naphthalein compounds toward Lactobacillus casei TS and hTS. The best TS inhibitors have been tested against a number of clinical isolates of Gram-positive-resistant bacterial strains. Compound 3,3-bis(3,5-dibromo-4-hydroxyphenyl)-1H, 3H-naphtho[1,2-c]furan-1-one(5) showed significant antibacterial activity, no in vitro toxicity, and dose-response effects against Staphylococcus epidermidis (MIC = 0.5-2.5 mu g/mL) clinical isolate strains, which are resistant to at least 17 of the best known antibacterial agents, including vancomycin. So far this compound can be regarded as a leading antibacterial agent.