[(2R,3R,4S,5S,6R)-6-(4-acetamidophenoxy)-3,4,5-triacetyloxyoxan-2-yl]methyl acetate | 1356585-83-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2R,3R,4S,5S,6R)-6-(4-acetamidophenoxy)-3,4,5-triacetyloxyoxan-2-yl]methyl acetate
• CAS: 1356585-83-5
• 化学式: C₂₂H₂₇NO₁₁
• 分子量: 481.456
• InChiKey: ZVFAHCKHVUBNMZ-AANPDWTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  153
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4S,5S,6R)-6-(4-acetamidophenoxy)-3,4,5-triacetyloxyoxan-2-yl]methyl acetate 在 甲醇 、 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 N-[4-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-tetrahydropyran-2-yl]oxyphenyl]acetamide
  参考文献：
  名称：

  Structure-Based Drug Design and Optimization of Mannoside Bacterial FimH Antagonists

  摘要：

  FimH-mediated cellular adhesion to mannosylated proteins is critical in the ability of uropathogenic E. coli (UPEC) to colonize and invade the bladder epithelium during urinary tract infection. We describe the discovery and optimization of potent small-molecule FimH bacterial adhesion antagonists based on alpha-D-mannose 1-position anomeric glycosides using X-ray structure-guided drug design. Optimized biarylmannosides display low nanomolar binding affinity for FimH in a fluorescence polarization assay and submicromolar cellular activity in a hemagglutination (HA) functional cell assay of bacterial adhesion. X-ray crystallography demonstrates that the biphenyl moiety makes several key interactions with the outer surface of FimH including pi-pi interactions with Tyr-48 and an H-bonding electrostatic interaction with the Arg-98/Glu-50 salt bridge. Dimeric analogues linked through the biaryl ring show an impressive 8-fold increase in potency relative to monomeric matched pairs and represent the most potent FimH antagonists identified to date. The FimH antagonists described herein hold great potential for development as novel therapeutics for the effective treatment of urinary tract infections.

  DOI：

  10.1021/jm100438s
• 作为产物：
  描述：

  对乙酰氨基酚 、 1,2,3,4,6-O-五乙酰基-Alpha-甘露糖 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 生成 [(2R,3R,4S,5S,6R)-6-(4-acetamidophenoxy)-3,4,5-triacetyloxyoxan-2-yl]methyl acetate
  参考文献：
  名称：

  Structure-Based Drug Design and Optimization of Mannoside Bacterial FimH Antagonists

  摘要：

  FimH-mediated cellular adhesion to mannosylated proteins is critical in the ability of uropathogenic E. coli (UPEC) to colonize and invade the bladder epithelium during urinary tract infection. We describe the discovery and optimization of potent small-molecule FimH bacterial adhesion antagonists based on alpha-D-mannose 1-position anomeric glycosides using X-ray structure-guided drug design. Optimized biarylmannosides display low nanomolar binding affinity for FimH in a fluorescence polarization assay and submicromolar cellular activity in a hemagglutination (HA) functional cell assay of bacterial adhesion. X-ray crystallography demonstrates that the biphenyl moiety makes several key interactions with the outer surface of FimH including pi-pi interactions with Tyr-48 and an H-bonding electrostatic interaction with the Arg-98/Glu-50 salt bridge. Dimeric analogues linked through the biaryl ring show an impressive 8-fold increase in potency relative to monomeric matched pairs and represent the most potent FimH antagonists identified to date. The FimH antagonists described herein hold great potential for development as novel therapeutics for the effective treatment of urinary tract infections.

  DOI：

  10.1021/jm100438s

文献信息

• GLYCOSYLATED ACETAMINOPHEN PRO-DRUG
  申请人：Shull Brian

  公开号：US20130217640A1

  公开（公告）日：2013-08-22

  The present invention relates to methods and compositions for the synthesis, production, and use of pro-drug analogs of the analgesic acetaminophen. This invention relates to a method for the production of a broad group of glycosides of acetaminophen derivatives.
• US8722864B2
  申请人：——

  公开号：US8722864B2

  公开（公告）日：2014-05-13