5,8-dioxo-1,4,4a,5,8,8a-hexahydronaphthalene-1-carboxylic acid | 6943-52-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5,8-dioxo-1,4,4a,5,8,8a-hexahydronaphthalene-1-carboxylic acid
• 英文别名: 5,8-diketo-1,4,4a,5,8,8a-hexahydronaphthalene-1-carboxylic acid；5-Hydroxy-8-oxo-1,4,4a,5,8,8a-hexahydro-naphthalin-1-carbonsaeure；5-Hydroxy-8-oxo-1,4,4a,5,8,8a-hexahydronaphthalene-1-carboxylic acid；5-hydroxy-8-oxo-4,4a,5,8a-tetrahydro-1H-naphthalene-1-carboxylic acid
• CAS: 6943-52-8
• 化学式: C₁₁H₁₂O₄
• 分子量: 208.214
• InChiKey: IZTKKSDDRFMLJJ-UHFFFAOYSA-N

物化性质

• 沸点：
  456.0±45.0 °C(Predicted)
• 密度：
  1.381±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  5,8-dioxo-1,4,4a,5,8,8a-hexahydronaphthalene-1-carboxylic acid 在 对甲苯磺酸 、 5%-palladium/activated carbon 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以75.4%的产率得到5,8-二羟基-1-萘甲酸 gamma-内酯
  参考文献：
  名称：

  2′-Deoxyuridine 5′-Monophosphate Substrate Displacement in Thymidylate Synthase through 6-Hydroxy-2H-naphtho[1,8-bc]furan-2-one Derivatives

  摘要：

  Thymidylate synthase (TS) is a target for antifolate-based chemotherapies of microbial and human diseases. Here, ligand-based, synthetic, and X-ray crystallography studies led to the discovery of 6-(3-cyanobenzoyloxy)-2-oxo-2H-naphto[1,8-bc]furan, a novel inhibitor with a K-i, of 310 nM against Pneumocystis carinii TS. The X-ray ternary complex with Escherichia coli TS revealed, for the first time, displacement of the substrate toward the dimeric protein interface, thus providing new opportunities for further design of specific inhibitors of microbial pathogens.

  DOI：

  10.1021/jm4014086
• 作为产物：
  描述：

  2,4-戊二烯酸 、 对苯醌 以 甲苯 为溶剂， 反应 24.0h， 以24%的产率得到5,8-dioxo-1,4,4a,5,8,8a-hexahydronaphthalene-1-carboxylic acid
  参考文献：
  名称：

  2′-Deoxyuridine 5′-Monophosphate Substrate Displacement in Thymidylate Synthase through 6-Hydroxy-2H-naphtho[1,8-bc]furan-2-one Derivatives

  摘要：

  Thymidylate synthase (TS) is a target for antifolate-based chemotherapies of microbial and human diseases. Here, ligand-based, synthetic, and X-ray crystallography studies led to the discovery of 6-(3-cyanobenzoyloxy)-2-oxo-2H-naphto[1,8-bc]furan, a novel inhibitor with a K-i, of 310 nM against Pneumocystis carinii TS. The X-ray ternary complex with Escherichia coli TS revealed, for the first time, displacement of the substrate toward the dimeric protein interface, thus providing new opportunities for further design of specific inhibitors of microbial pathogens.

  DOI：

  10.1021/jm4014086

文献信息

• 2′-Deoxyuridine 5′-Monophosphate Substrate Displacement in Thymidylate Synthase through 6-Hydroxy-2<i>H</i>-naphtho[1,8-<i>bc</i>]furan-2-one Derivatives
  作者：Stefania Ferrari、Samuele Calò、Rosalida Leone、Rosaria Luciani、Luca Costantino、Susan Sammak、Flavio Di Pisa、Cecilia Pozzi、Stefano Mangani、M. Paola Costi

  DOI：10.1021/jm4014086

  日期：2013.11.27

  Thymidylate synthase (TS) is a target for antifolate-based chemotherapies of microbial and human diseases. Here, ligand-based, synthetic, and X-ray crystallography studies led to the discovery of 6-(3-cyanobenzoyloxy)-2-oxo-2H-naphto[1,8-bc]furan, a novel inhibitor with a K-i, of 310 nM against Pneumocystis carinii TS. The X-ray ternary complex with Escherichia coli TS revealed, for the first time, displacement of the substrate toward the dimeric protein interface, thus providing new opportunities for further design of specific inhibitors of microbial pathogens.