(3aR,4R,7aS)-hexahydro-2H-furo[2,3-b]pyran-4-yl-(4-nitrophenyl)carbonate | 1262482-40-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡喃类
• 英文名称: (3aR,4R,7aS)-hexahydro-2H-furo[2,3-b]pyran-4-yl-(4-nitrophenyl)carbonate
• 英文别名: [(3aR,4R,7aS)-3,3a,4,5,6,7a-hexahydro-2H-furo[2,3-b]pyran-4-yl] (4-nitrophenyl) carbonate
• CAS: 1262482-40-5
• 化学式: C₁₄H₁₅NO₇
• 分子量: 309.276
• InChiKey: PZVXZMVLCGWMBO-UPJWGTAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3aR,4R,7aS)-hexahydro-2H-furo[2,3-b]pyran-4-yl-(4-nitrophenyl)carbonate 、 N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-methoxybenzenesulfonamide 在 三乙胺 作用下， 以 乙腈 为溶剂， 生成 (3aR,4R,7aS)-hexahydro-2H-furo[2,3-b]pyran-4-yl-((2S,3R)-3-Hydroxy-4-(N-isobutyl-4-methoxyphenylsulfonamido)-1-phenylbutan-2-yl)carbamate
  参考文献：
  名称：

  Design and Synthesis of Potent HIV-1 Protease Inhibitors Incorporating Hexahydrofuropyranol-Derived High Affinity P₂ Ligands: Structure−Activity Studies and Biological Evaluation

  摘要：

  The design, synthesis, and evaluation of a new series of hexahydrofuropyranol-derived HIV-1 protease inhibitors are described. We have designed a stereochemically defined hexahydrofuropyranol-derived urethane as the P2-ligand. The current ligand is designed based upon the X-ray structure of la-bound HIV-1 protease. The synthesis of (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-ol, (-)-7, was carried out in optically active form. Incorporation of this ligand provided inhibitor 35a, which has shown excellent enzyme inhibitory activity and antiviral potency. Our structure activity studies have indicated that the stereochemistry and the position of oxygens in the ligand are important to the observed potency of the inhibitor. Inhibitor 35a has maintained excellent potency against multidrug-resistant HIV-1 variants. An active site model of 35a was created based upon the X-ray structure of 1b-bound HIV-1 protease. The model offers molecular insights regarding ligand-binding site interactions of the hexahydrofuropyranol-derived novel P2-ligand.

  DOI：

  10.1021/jm1012787
• 作为产物：
  描述：

  (4R,4aR,7aS)-4-(tert-butyldimethylsilyloxy)hexahydrofuro-[2,3-b]pyrane 在 吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (3aR,4R,7aS)-hexahydro-2H-furo[2,3-b]pyran-4-yl-(4-nitrophenyl)carbonate
  参考文献：
  名称：

  Design and Synthesis of Potent HIV-1 Protease Inhibitors Incorporating Hexahydrofuropyranol-Derived High Affinity P₂ Ligands: Structure−Activity Studies and Biological Evaluation

  摘要：

  The design, synthesis, and evaluation of a new series of hexahydrofuropyranol-derived HIV-1 protease inhibitors are described. We have designed a stereochemically defined hexahydrofuropyranol-derived urethane as the P2-ligand. The current ligand is designed based upon the X-ray structure of la-bound HIV-1 protease. The synthesis of (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-ol, (-)-7, was carried out in optically active form. Incorporation of this ligand provided inhibitor 35a, which has shown excellent enzyme inhibitory activity and antiviral potency. Our structure activity studies have indicated that the stereochemistry and the position of oxygens in the ligand are important to the observed potency of the inhibitor. Inhibitor 35a has maintained excellent potency against multidrug-resistant HIV-1 variants. An active site model of 35a was created based upon the X-ray structure of 1b-bound HIV-1 protease. The model offers molecular insights regarding ligand-binding site interactions of the hexahydrofuropyranol-derived novel P2-ligand.

  DOI：

  10.1021/jm1012787