(S)-3-(3-nitrophenyl)-2-oxooxazolidine-5-carboxylic acid | 1255517-34-0

• 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: (S)-3-(3-nitrophenyl)-2-oxooxazolidine-5-carboxylic acid
• 英文别名: (5S)-3-(3-nitrophenyl)-2-oxo-1,3-oxazolidine-5-carboxylic acid
• CAS: 1255517-34-0
• 化学式: C₁₀H₈N₂O₆
• 分子量: 252.183
• InChiKey: XTGLTTYXMJTZDA-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-3-(3-nitrophenyl)-2-oxooxazolidine-5-carboxylic acid 在 草酰氯 作用下， 生成 (5S)-3-(3-nitrophenyl)-2-oxo-1,3-oxazolidine-5-carbonyl chloride
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Structure−Activity Relationship Studies of HIV-1 Protease Inhibitors Incorporating Phenyloxazolidinones

  摘要：

  A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds with 2- and 4-substituted phenyloxazolidinones at P2 exhibited lower binding affinities than 3-substituted analogues. Crystal structure analyses of ligand-enzyme complexes revealed different binding modes for 2- and 3-substituted P2 moieties in the protease S2 binding pocket, which may explain their different binding affinities. Several compounds with 3-substituted P2 moieties demonstrated picomolar binding affinity and low nanomolar antiviral potency against patient-derived viruses from HIV-1 clades A, B, and C, and most retained potency against drug-resistant viruses. Further optimization of these compounds using structure-based design may lead to the development of novel protease inhibitors with improved activity against drug-resistant strains of HIV-1.

  DOI：

  10.1021/jm1008743
• 作为产物：
  描述：

  (S)-5-(hydroxymethyl)-3-(3-nitrophenyl)oxazolidin-2-one 在 sodium periodate 、 水 作用下， 以 四氯化碳 、 水 、 乙腈 为溶剂， 以83%的产率得到(S)-3-(3-nitrophenyl)-2-oxooxazolidine-5-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Structure−Activity Relationship Studies of HIV-1 Protease Inhibitors Incorporating Phenyloxazolidinones

  摘要：

  A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds with 2- and 4-substituted phenyloxazolidinones at P2 exhibited lower binding affinities than 3-substituted analogues. Crystal structure analyses of ligand-enzyme complexes revealed different binding modes for 2- and 3-substituted P2 moieties in the protease S2 binding pocket, which may explain their different binding affinities. Several compounds with 3-substituted P2 moieties demonstrated picomolar binding affinity and low nanomolar antiviral potency against patient-derived viruses from HIV-1 clades A, B, and C, and most retained potency against drug-resistant viruses. Further optimization of these compounds using structure-based design may lead to the development of novel protease inhibitors with improved activity against drug-resistant strains of HIV-1.

  DOI：

  10.1021/jm1008743

文献信息

• Structure-Based Design, Synthesis, and Structure−Activity Relationship Studies of HIV-1 Protease Inhibitors Incorporating Phenyloxazolidinones
  作者：Akbar Ali、G. S. Kiran Kumar Reddy、Madhavi N. L. Nalam、Saima Ghafoor Anjum、Hong Cao、Celia A. Schiffer、Tariq M. Rana

  DOI：10.1021/jm1008743

  日期：2010.11.11

  A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds with 2- and 4-substituted phenyloxazolidinones at P2 exhibited lower binding affinities than 3-substituted analogues. Crystal structure analyses of ligand-enzyme complexes revealed different binding modes for 2- and 3-substituted P2 moieties in the protease S2 binding pocket, which may explain their different binding affinities. Several compounds with 3-substituted P2 moieties demonstrated picomolar binding affinity and low nanomolar antiviral potency against patient-derived viruses from HIV-1 clades A, B, and C, and most retained potency against drug-resistant viruses. Further optimization of these compounds using structure-based design may lead to the development of novel protease inhibitors with improved activity against drug-resistant strains of HIV-1.