o-chloro-p-[N-(2-ethoxy-3,4-dioxocyclobut-1-enyl)amino]phenyl α-D-mannopyranoside | 916849-17-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: o-chloro-p-[N-(2-ethoxy-3,4-dioxocyclobut-1-enyl)amino]phenyl α-D-mannopyranoside
• 英文别名: 2-chloro-4-[(2-ethoxy-3,4-dioxocyclobuten-1-yl)amino]phenyl α-D-mannopyranoside；3-[[3-Chloro-4-(I+/--D-mannopyranosyloxy)phenyl]amino]-4-ethoxy-3-cyclobutene-1,2-dione；3-[3-chloro-4-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyanilino]-4-ethoxycyclobut-3-ene-1,2-dione
• CAS: 916849-17-7
• 化学式: C₁₈H₂₀ClNO₉
• 分子量: 429.811
• InChiKey: YWFQHAGJFOJHHY-GNELUTOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  155
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 o-chloro-p-[N-(2-ethoxy-3,4-dioxocyclobut-1-enyl)amino]phenyl α-D-mannopyranoside 在 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以90%的产率得到2-chloro-4-[(2-(4-methylpiperazin-1-yl)-3,4-dioxocyclobuten-1-yl)amino]phenyl α-D-mannopyranoside
  参考文献：
  名称：

  Target Selectivity of FimH Antagonists

  摘要：

  Mannose-based FimH antagonists are considered new therapeutics for the treatment of urinary tract. infections (UTIs). They prevent the adhesion of uropathogenic Escherichia coli (UPEC) to urothelial cell surfaces triggered by the lectin FimH, which is located at the tip of bacterial type I pili. Because all reported FimH antagonists are alpha-D-mannosides, they are also potential ligands of mannose receptors of the human host system. We therefore investigated the selectivity range of five FimH antagonists belonging to different compound families by comparing their affinities for FimH and eight human mannose receptors. On the basis of the detected selectivity range of approximately 5 orders of magnitude, no adverse side effects resulting from nonselective binding to the human receptors have to be expected. FimH antagonists can therefore be further considered as potential therapeutics for the., treatment of UTI.

  DOI：

  10.1021/jm3010338
• 作为产物：
  描述：

  2-氯-4-硝基苯基-a-D-吡喃甘露糖苷 在 吗啉 、 platinum(IV) oxide 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 24.75h， 生成 o-chloro-p-[N-(2-ethoxy-3,4-dioxocyclobut-1-enyl)amino]phenyl α-D-mannopyranoside
  参考文献：
  名称：

  Target Selectivity of FimH Antagonists

  摘要：

  Mannose-based FimH antagonists are considered new therapeutics for the treatment of urinary tract. infections (UTIs). They prevent the adhesion of uropathogenic Escherichia coli (UPEC) to urothelial cell surfaces triggered by the lectin FimH, which is located at the tip of bacterial type I pili. Because all reported FimH antagonists are alpha-D-mannosides, they are also potential ligands of mannose receptors of the human host system. We therefore investigated the selectivity range of five FimH antagonists belonging to different compound families by comparing their affinities for FimH and eight human mannose receptors. On the basis of the detected selectivity range of approximately 5 orders of magnitude, no adverse side effects resulting from nonselective binding to the human receptors have to be expected. FimH antagonists can therefore be further considered as potential therapeutics for the., treatment of UTI.

  DOI：

  10.1021/jm3010338

文献信息

• Evaluation of the carbohydrate recognition domain of the bacterial adhesin FimH: design, synthesis and binding properties of mannoside ligands
  作者：Oliver Sperling、Andreas Fuchs、Thisbe K. Lindhorst

  DOI：10.1039/b610745a

  日期：——

  Fimbriae are proteinogeneous appendages on the surface of bacteria, which mediate bacterial adhesion to the host cell glycocalyx. The so-called type 1 fimbriae exhibit specificity for α-D-mannosides and, therefore, they are assumed to mediate bacterial adhesion via the interaction of a fimbrial lectin and α-D-mannosyl residues exposed on the host cell surface. This carbohydrate-specific adhesive protein subunit of type 1 fimbriae has been identified as a protein called FimH. The crystal structure of this lectin is known and, based on this information, the molecular details of the interaction of mannoside ligands and FimH are addressed in this paper. Computer-based docking methods were used to evaluate known ligands as well as to design new ones. Then, a series of new mannosides with extended aglycon was synthesized and tested as inhibitors of type 1 fimbriae-mediated bacterial adhesion in an ELISA. The results obtained were compared to the predictions and findings as delivered by molecular modeling. This study led to an improved understanding of the ligand–receptor interactions under investigation.

  菌毛是细菌表面的一种蛋白质衍生附属物，介导细菌与宿主细胞糖萼的粘附。所谓的一型菌毛对α-D-甘露糖苷具有特异性，因此假设它们通过菌毛凝集素与宿主细胞表面暴露的α-D-甘露糖基残基的相互作用来介导细菌粘附。这种一型菌毛的糖类特异性粘附蛋白亚单位已被鉴定为一种称为FimH的蛋白质。这种凝集素的晶体结构是已知的，基于这些信息，本文详细讨论了甘露糖苷配体与FimH相互作用的分子细节。使用基于计算机的对接方法来评估已知配体并设计新的配体。然后，合成了一系列具有扩展配基的新型甘露糖苷，并作为一型菌毛介导细菌粘附的抑制剂在ELISA中进行了测试。获得的实验结果与分子建模提供的预测和发现进行了比较。这项研究提高了对所研究配体-受体相互作用的理解。
• Target Selectivity of FimH Antagonists
  作者：Meike Scharenberg、Oliver Schwardt、Said Rabbani、Beat Ernst

  DOI：10.1021/jm3010338

  日期：2012.11.26

  Mannose-based FimH antagonists are considered new therapeutics for the treatment of urinary tract. infections (UTIs). They prevent the adhesion of uropathogenic Escherichia coli (UPEC) to urothelial cell surfaces triggered by the lectin FimH, which is located at the tip of bacterial type I pili. Because all reported FimH antagonists are alpha-D-mannosides, they are also potential ligands of mannose receptors of the human host system. We therefore investigated the selectivity range of five FimH antagonists belonging to different compound families by comparing their affinities for FimH and eight human mannose receptors. On the basis of the detected selectivity range of approximately 5 orders of magnitude, no adverse side effects resulting from nonselective binding to the human receptors have to be expected. FimH antagonists can therefore be further considered as potential therapeutics for the., treatment of UTI.