(2R,3S,4S,5S,6R)-2-(hydroxymethyl)-6-(2-phenylphenoxy)-tetrahydropyran-3,4,5-triol

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3S,4S,5S,6R)-2-(hydroxymethyl)-6-(2-phenylphenoxy)-tetrahydropyran-3,4,5-triol
• 英文别名: 2-(hydroxymethyl)-6-(2-phenylphenoxy)tetrahydropyran-3,4,5-triol；(2R,3S,4S,5S,6R)-2-(hydroxymethyl)-6-(2-phenylphenoxy)oxane-3,4,5-triol
• 化学式: C₁₈H₂₀O₆
• 分子量: 332.353
• InChiKey: CDHOJFZUDDYXIG-ZBRFXRBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  99.4
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  邻苯基苯酚 在 lithium hydroxide 、 三氟化硼乙醚 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 生成 (2R,3S,4S,5S,6R)-2-(hydroxymethyl)-6-(2-phenylphenoxy)-tetrahydropyran-3,4,5-triol
  参考文献：
  名称：

  Rational Design and Synthesis of Small Molecule, Non-oligosaccharide Selectin Inhibitors: (.alpha.-D-Mannopyranosyloxy)biphenyl-Substituted Carboxylic Acids

  摘要：

  The calcium dependent E-selectin/sialyl Lewis(x) (sLe(x)) interaction plays a key role in inflammation where it mediates the rolling of leukocytes prior to firm adhesion and extravasation from the vasculature. A model of E-selectin/sLe(x) binding, along with previously reported structure-activity relationships of sLe(x)-related oligosaccharide, was used in the rational design of non-oligosaccharide inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling (Suzuki) reaction was used as the key step to prepare a number of substituted biphenyls which were assayed for their ability to inhibit the binding of E-, P-, and L-selectin-IgG fusion proteins to sLe(x) expressed on the surface of HL60 cells. Some of the compounds developed had greater in vitro potency than the parent sLe(x) tetrasaccharide and are currently being evaluated in in vivo models of inflammation to select a candidate for clinical development.

  DOI：

  10.1021/jm00026a004

文献信息

• Structure-Based Drug Design and Optimization of Mannoside Bacterial FimH Antagonists
  作者：Zhenfu Han、Jerome S. Pinkner、Bradley Ford、Robert Obermann、William Nolan、Scott A. Wildman、Doug Hobbs、Tom Ellenberger、Corinne K. Cusumano、Scott J. Hultgren、James W. Janetka

  DOI：10.1021/jm100438s

  日期：2010.6.24

  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.