3,3-bis-(4-hydroxyl-5-isopropyl-2-methylphenyl)-3H-naphtho(1,2-c)furan-1-one

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3,3-bis-(4-hydroxyl-5-isopropyl-2-methylphenyl)-3H-naphtho(1,2-c)furan-1-one
• 英文别名: 3,3-bis-(4-hydroxy-5-isopropyl-2-methylphenyl)-3H-naphtho[1,2-c]furan-1-one；1,1-Bis(4-hydroxy-5-isopropyl-2-methyl-phenyl)benzo[e]isobenzofuran-3-one；1,1-bis(4-hydroxy-2-methyl-5-propan-2-ylphenyl)benzo[e][2]benzofuran-3-one
• 化学式: C₃₂H₃₂O₄
• 分子量: 480.604
• InChiKey: ZVPGVHLZYWNODB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,2-萘二酸酐 、 百里酚 在 aluminum (III) chloride 作用下， 以 tetrachloroethanol 为溶剂， 以6%的产率得到3,3-bis-(4-hydroxyl-5-isopropyl-2-methylphenyl)-3H-naphtho(1,2-c)furan-1-one
  参考文献：
  名称：

  Naphthofuranone Derivatives as Specific Inhibitors of Thymidylate Synthases

  摘要：

  本发明揭示了具有特定抑制细菌种类嘧啶核苷酸合成酶酶活性的1,2-萘醌分子(I)的合成化合物，其制备方法，药用组合物以及在治疗和预防感染性病理中的应用。

  公开号：

  US20100048692A1

文献信息

• Naphthofuranone Derivatives as Specific Inhibitors of Thymidylate Synthases
  申请人：Venturelli Alberto

  公开号：US20100048692A1

  公开（公告）日：2010-02-25

  Synthetic compounds of 1,2-naphthalein moelcules (I) having specific inhibitory properties of the enzymatic activity of thymidylate synthases of bacterial species, their preparation, their pharmaceutical composition and use in the treatment and prophylaxis of infectious pathologies are disclosed.

  本发明揭示了具有特定抑制细菌种类嘧啶核苷酸合成酶酶活性的1,2-萘醌分子(I)的合成化合物，其制备方法，药用组合物以及在治疗和预防感染性病理中的应用。
• WO2008/3510
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.