3-phenylpropyl 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranoside | 1259428-64-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3-phenylpropyl 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranoside
• 英文别名: [(2R,3R,4S,5S,6S)-3,4,5-tribenzoyloxy-6-(3-phenylpropoxy)oxan-2-yl]methyl benzoate
• CAS: 1259428-64-2
• 化学式: C₄₃H₃₈O₁₀
• 分子量: 714.769
• InChiKey: WOKXNKISOWPHHC-ALKPXMPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  53
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-phenylpropyl 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranoside 在 甲醇 、 sodium methylate 作用下， 以48%的产率得到3-phenylpropyl α-D-mannopyranoside
  参考文献：
  名称：

  FimH Antagonists for the Oral Treatment of Urinary Tract Infections: From Design and Synthesis to in Vitro and in Vivo Evaluation

  摘要：

  Urinary tract infection (UTI) by uropathogenic Escherichia coli (UPEC) is one of the most common infections, particularly affecting women. The interaction of FimH, a lectin located at the tip of bacterial pill, with high mannose structures is critical for the ability of UPEC to colonize and invade the bladder epithelium. We describe the synthesis and the in vitro/in vivo evaluation of alpha-D-mannosides with the ability to block the bacteria/host cell interaction. According to the pharmacokinetic properties, a prodrug approach for their evaluation in the UTI mouse model was explored. As a result, an orally available, low molecular weight FimH antagonist was identified with the potential to reduce the colony forming units (CFU) in the urine by 2 orders of magnitude and in the bladder by 4 orders of magnitude. With FimH antagonist 16b, the great potential for the effective treatment of urinary tract infections with a new class of orally available antiinfectives could be demonstrated.

  DOI：

  10.1021/jm101011y
• 作为产物：
  描述：

  2,3,4,6-Tetra-O-benzoyl-α-D-mannopyranosyl bromide 、 3-苯丙醇 在 mercury(II) cyanide 、 mercury dibromide 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以57%的产率得到3-phenylpropyl 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranoside
  参考文献：
  名称：

  FimH Antagonists for the Oral Treatment of Urinary Tract Infections: From Design and Synthesis to in Vitro and in Vivo Evaluation

  摘要：

  Urinary tract infection (UTI) by uropathogenic Escherichia coli (UPEC) is one of the most common infections, particularly affecting women. The interaction of FimH, a lectin located at the tip of bacterial pill, with high mannose structures is critical for the ability of UPEC to colonize and invade the bladder epithelium. We describe the synthesis and the in vitro/in vivo evaluation of alpha-D-mannosides with the ability to block the bacteria/host cell interaction. According to the pharmacokinetic properties, a prodrug approach for their evaluation in the UTI mouse model was explored. As a result, an orally available, low molecular weight FimH antagonist was identified with the potential to reduce the colony forming units (CFU) in the urine by 2 orders of magnitude and in the bladder by 4 orders of magnitude. With FimH antagonist 16b, the great potential for the effective treatment of urinary tract infections with a new class of orally available antiinfectives could be demonstrated.

  DOI：

  10.1021/jm101011y

文献信息

• FimH Antagonists for the Oral Treatment of Urinary Tract Infections: From Design and Synthesis to in Vitro and in Vivo Evaluation
  作者：Tobias Klein、Daniela Abgottspon、Matthias Wittwer、Said Rabbani、Janno Herold、Xiaohua Jiang、Simon Kleeb、Christine Lüthi、Meike Scharenberg、Jacqueline Bezençon、Erich Gubler、Lijuan Pang、Martin Smiesko、Brian Cutting、Oliver Schwardt、Beat Ernst

  DOI：10.1021/jm101011y

  日期：2010.12.23

  Urinary tract infection (UTI) by uropathogenic Escherichia coli (UPEC) is one of the most common infections, particularly affecting women. The interaction of FimH, a lectin located at the tip of bacterial pill, with high mannose structures is critical for the ability of UPEC to colonize and invade the bladder epithelium. We describe the synthesis and the in vitro/in vivo evaluation of alpha-D-mannosides with the ability to block the bacteria/host cell interaction. According to the pharmacokinetic properties, a prodrug approach for their evaluation in the UTI mouse model was explored. As a result, an orally available, low molecular weight FimH antagonist was identified with the potential to reduce the colony forming units (CFU) in the urine by 2 orders of magnitude and in the bladder by 4 orders of magnitude. With FimH antagonist 16b, the great potential for the effective treatment of urinary tract infections with a new class of orally available antiinfectives could be demonstrated.