1-[3-chloro-4-(α-D-mannopyranosyloxy)phenyl]-1H-indole-5-carboxylic acid | 1375142-17-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[3-chloro-4-(α-D-mannopyranosyloxy)phenyl]-1H-indole-5-carboxylic acid
• 英文别名: 1-[3-chloro-4-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]indole-5-carboxylic acid
• CAS: 1375142-17-8
• 化学式: C₂₁H₂₀ClNO₈
• 分子量: 449.845
• InChiKey: UPSQJAOEPOVWAK-AGRFSFNASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  142
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  benzyl 1H-indole-5-carboxylate 在 potassium phosphate 、 trans cyclohexane-1,2-diamine 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 2.0h， 生成 1-[3-chloro-4-(α-D-mannopyranosyloxy)phenyl]-1H-indole-5-carboxylic acid
  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

文献信息

• Mannose-derived antagonists of FimH useful for treating disease
  申请人：Fimbrion Therapeutics, Inc.

  公开号：US10738070B2

  公开（公告）日：2020-08-11

  The present invention relates to mannoside derivative compounds useful as inhibitors of FimH and methods for the treatment or prevention of urinary tract infection.

  本发明涉及可用作 FimH 抑制剂的甘露糖苷衍生物化合物以及治疗或预防尿路感染的方法。
• MANNOSE-DERIVED ANTAGONISTS OF FIMH USEFUL FOR TREATING DISEASE
  申请人：Fimbrion Therapeutics, Inc.

  公开号：US20190106451A1

  公开（公告）日：2019-04-11

  The present invention relates to mannoside derivative compounds useful as inhibitors of FimH and methods for the treatment or prevention of urinary tract infection.
• Antiadhesion Therapy for Urinary Tract Infections—A Balanced PK/PD Profile Proved To Be Key for Success
  作者：Xiaohua Jiang、Daniela Abgottspon、Simon Kleeb、Said Rabbani、Meike Scharenberg、Matthias Wittwer、Martina Haug、Oliver Schwardt、Beat Ernst

  DOI：10.1021/jm300192x

  日期：2012.5.24

  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).