(2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-(2-fluoro-4-(5-nitro-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 1312312-63-2

• 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)-2-(acetoxymethyl)-6-(2-fluoro-4-(5-nitro-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• CAS: 1312312-63-2
• 化学式: C₂₈H₂₇FN₂O₁₂
• 分子量: 602.527
• InChiKey: VSGQOZIBBXZQBM-MASCHLQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.14
• 重原子数：
  43.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  171.73
• 氢给体数：
  0.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-(2-fluoro-4-(5-nitro-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 甲醇 、 sodium methylate 作用下， 以45 mg的产率得到2-fluoro-4-(5-nitroindol-1-yl)phenyl α-D-mannopyranoside
  参考文献：
  名称：

  Antiadhesion Therapy for Urinary Tract Infections—A Balanced PK/PD Profile Proved To Be Key for Success

  摘要：

  The initial step for the successful establishment of urinary tract infections (UTIs), predominantly caused by uropathogenic Escherichia coli, is the adhesion of bacteria to urothelial cells. This attachment is mediated by FimH, a mannose-binding adhesin, which is expressed on the bacterial surface. To date, UTIs are mainly treated with antibiotics, leading to the ubiquitous problem of increasing resistance against most of the currently available antimicrobials. Therefore, new treatment strategies are urgently needed, avoiding selection pressure and thereby implying a reduced risk of resistance. Here, we present a new class of highly active antimicrobials, targeting the virulence factor FimH. When the most potent representative, an indolinylphenyl mannoside, was administered in a mouse model at the low dosage of 1 mg/kg (corresponding to approximately 25 mu g/mouse), the minimal therapeutic concentration to prevent UTI was maintained for more than 8 h. In a treatment study, the colony-forming units in the bladder could be reduced by almost 4 orders of magnitude, comparable to the standard antibiotic treatment with ciprofloxacin (8 mg/kg, sc).

  DOI：

  10.1021/jm300192x
• 作为产物：
  描述：

  2-氟-4-碘苯酚 在 potassium phosphate 、 trans cyclohexane-1,2-diamine 、 三氟甲磺酸三甲基硅酯 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 4.0h， 生成 (2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-(2-fluoro-4-(5-nitro-1H-indol-1-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  Antiadhesion Therapy for Urinary Tract Infections—A Balanced PK/PD Profile Proved To Be Key for Success

  摘要：

  The initial step for the successful establishment of urinary tract infections (UTIs), predominantly caused by uropathogenic Escherichia coli, is the adhesion of bacteria to urothelial cells. This attachment is mediated by FimH, a mannose-binding adhesin, which is expressed on the bacterial surface. To date, UTIs are mainly treated with antibiotics, leading to the ubiquitous problem of increasing resistance against most of the currently available antimicrobials. Therefore, new treatment strategies are urgently needed, avoiding selection pressure and thereby implying a reduced risk of resistance. Here, we present a new class of highly active antimicrobials, targeting the virulence factor FimH. When the most potent representative, an indolinylphenyl mannoside, was administered in a mouse model at the low dosage of 1 mg/kg (corresponding to approximately 25 mu g/mouse), the minimal therapeutic concentration to prevent UTI was maintained for more than 8 h. In a treatment study, the colony-forming units in the bladder could be reduced by almost 4 orders of magnitude, comparable to the standard antibiotic treatment with ciprofloxacin (8 mg/kg, sc).

  DOI：

  10.1021/jm300192x