(hydroxy(3-(3-phenoxyphenyl)propyl)phosphoryl)methylphosphonic acid | 1160907-49-2

• 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: (hydroxy(3-(3-phenoxyphenyl)propyl)phosphoryl)methylphosphonic acid
• 英文别名: [Hydroxy-[4-(3-phenoxyphenyl)butyl]phosphoryl]methylphosphonic acid
• CAS: 1160907-49-2
• 化学式: C₁₇H₂₂O₆P₂
• 分子量: 384.306
• InChiKey: RTCPZTIXSJDGSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (hydroxy(3-(3-phenoxyphenyl)propyl)phosphoryl)methylphosphonic acid 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 以320 mg的产率得到(hydroxy(3-(3-phenoxyphenyl)propyl)phosphoryl)methylphosphonic acid tripotassium salt
  参考文献：
  名称：

  Inhibition of Staphyloxanthin Virulence Factor Biosynthesis in Staphylococcus aureus: In Vitro, in Vivo, and Crystallographic Results

  摘要：

  The gold color of Staphylococcus aureus is derived from the carotenoid staphyloxanthin, a virulence factor for the organism. Here, we report the synthesis and activity of a broad variety of staphyloxanthin biosynthesis inhibitors that inhibit the first committed step in its biosynthesis, condensation of two farnesyl diphosphate (FPP) molecules to dehydrosqualene, catalyzed by the enzyme dehydrosqualene synthase (CrtM). The most active compounds are phosphonoacetamides that have low nanomolar K-i values for CrtM inhibition and are active in whole bacterial cells and in mice, where they inhibit S. aureus disease progression. We also report the X-ray crystallographic structure of the most active compound, N-3-(3-phenoxyphenyl)propylphosphonoacetamide (IC50 = 8 nM, in cells), bound to CrtM. The structure exhibits a complex network of hydrogen bonds between the polar headgroup and the protein, while the 3-phenoxyphenyl side chain is located in a hydrophobic pocket previously reported to bind farnesyl thiodiphosphate (FsPP), as well as biphenyl phosphonosulfonate inhibitors. Given the good enzymatic, whole cell, and in vivo pharmacologic activities, these results should help guide the further development of novel antivirulence factor-based therapies for S. aureus infections.

  DOI：

  10.1021/jm9001764
• 作为产物：
  描述：

  1-[4-[Diethoxyphosphorylmethyl(ethoxy)phosphoryl]butyl]-3-phenoxybenzene 在 三甲基溴硅烷 、 甲醇 作用下， 以 乙腈 为溶剂， 反应 6.0h， 生成 (hydroxy(3-(3-phenoxyphenyl)propyl)phosphoryl)methylphosphonic acid
  参考文献：
  名称：

  Inhibition of Staphyloxanthin Virulence Factor Biosynthesis in Staphylococcus aureus: In Vitro, in Vivo, and Crystallographic Results

  摘要：

  The gold color of Staphylococcus aureus is derived from the carotenoid staphyloxanthin, a virulence factor for the organism. Here, we report the synthesis and activity of a broad variety of staphyloxanthin biosynthesis inhibitors that inhibit the first committed step in its biosynthesis, condensation of two farnesyl diphosphate (FPP) molecules to dehydrosqualene, catalyzed by the enzyme dehydrosqualene synthase (CrtM). The most active compounds are phosphonoacetamides that have low nanomolar K-i values for CrtM inhibition and are active in whole bacterial cells and in mice, where they inhibit S. aureus disease progression. We also report the X-ray crystallographic structure of the most active compound, N-3-(3-phenoxyphenyl)propylphosphonoacetamide (IC50 = 8 nM, in cells), bound to CrtM. The structure exhibits a complex network of hydrogen bonds between the polar headgroup and the protein, while the 3-phenoxyphenyl side chain is located in a hydrophobic pocket previously reported to bind farnesyl thiodiphosphate (FsPP), as well as biphenyl phosphonosulfonate inhibitors. Given the good enzymatic, whole cell, and in vivo pharmacologic activities, these results should help guide the further development of novel antivirulence factor-based therapies for S. aureus infections.

  DOI：

  10.1021/jm9001764

文献信息

• ANTI-BACTERIAL COMPOSITIONS AND METHODS INCLUDING TARGETING VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS
  申请人：Oldfield Eric

  公开号：US20120022024A1

  公开（公告）日：2012-01-26

  This disclosure relates to compositions and methods including for the inhibition, prevention, and/or treatment of microbial infections, including infections from such pathogens as Staphylococcus aureus.

  本公开涉及包括用于抑制、预防和/或治疗微生物感染的组合物和方法，包括对金黄色葡萄球菌等病原体引起的感染。