methyl 2',6'-dichloro-4'-(α-D-mannopyranosyloxy)-biphenyl-4-carboxylate | 1259428-84-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2',6'-dichloro-4'-(α-D-mannopyranosyloxy)-biphenyl-4-carboxylate
• 英文别名: Methyl 2',6'-dichloro-4'-(alpha-D-mannopyranosyloxy)-biphenyl-4-carboxylate；methyl 4-[2,6-dichloro-4-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]benzoate
• CAS: 1259428-84-6
• 化学式: C₂₀H₂₀Cl₂O₈
• 分子量: 459.28
• InChiKey: PRHJCSVIPWVXNC-XMUPAAEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 2',6'-dichloro-4'-(α-D-mannopyranosyloxy)-biphenyl-4-carboxylate 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 24.0h， 以75%的产率得到sodium 2',6'-dichloro-4'-(α-D-mannopyranosyloxy)-biphenyl-4-carboxylate
  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：

  methyl 4'-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyloxy)-2',6'-dichlorobiphenyl-4-carboxylate 在 水合甲醇 作用下， 以 甲醇 、 sodium methylate 为溶剂， 反应 24.0h， 以to yield 7d (29 mg, 77%) as a white solid的产率得到methyl 2',6'-dichloro-4'-(α-D-mannopyranosyloxy)-biphenyl-4-carboxylate
  参考文献：
  名称：

  MANNOSE DERIVATIVES AS ANTAGONISTS OF BACTERIAL ADHESION

  摘要：

  式(I)的化合物，其中n为0、1或2，R1为芳基、杂芳基或杂环基，R2和R3为氢或规范中所述的取代基，对于预防和治疗细菌感染，特别是由大肠杆菌引起的尿路感染是有用的。

  公开号：

  US20120270824A1

文献信息

• MANNOSE DERIVATIVES AS ANTAGONISTS OF BACTERIAL ADHESION
  申请人：Ernst Beat

  公开号：US20120270824A1

  公开（公告）日：2012-10-25

  Compounds of the formula (I) wherein n is 0, 1 or 2, R 1 is aryl, heteroaryl or heterocyclyl, and R 2 and R 3 are hydrogen or a substituent as described in the specification, are useful for the prevention and treatment of bacterial infections, in particular of urinary infections caused by E. coli .

  式(I)的化合物，其中n为0、1或2，R1为芳基、杂芳基或杂环基，R2和R3为氢或规范中所述的取代基，对于预防和治疗细菌感染，特别是由大肠杆菌引起的尿路感染是有用的。
• Mannose derivatives as antagonists of bacterial adhesion
  申请人：University of Basel

  公开号：EP2604619A2

  公开（公告）日：2013-06-19

  Compounds of the formula (I) wherein n is 0, 1 or 2, R1 is aryl, heteroaryl or heterocyclyl, and R2 and R3 are hydrogen or a substituent as described in the specification, are useful for the prevention and treatment of bacterial infections, in particular of urinary infections caused by E. coli.

  式 (I) 的化合物 其中 n 为 0、1 或 2，R1 为芳基、杂芳基或杂环基，R2 和 R3 为氢或说明书中所述的取代基，可用于预防和治疗细菌感染，特别是由大肠杆菌引起的泌尿系统感染。
• PHENYL-ALPHA-D-MANNOSIDES FOR USE IN THE TREATMENT OF BACTERIAL INFECTIONS CAUSED BY ESCHERICHIA COLI
  申请人：University of Basel

  公开号：EP2960247A1

  公开（公告）日：2015-12-30

  Compounds of the formula (I) wherein n is 0, 1 or 2, R2 and R3 are hydrogen or a substituent as described in the specification, are useful for the prevention and treatment of bacterial infections, in particular of urinary infections caused by E. coli, wherein R1 is one of groups (B), (C), (D), (E) below:

  式（I）化合物，其中 n 为 0、1 或 2，R2 和 R3 为氢或说明书中所述的取代基，可用于预防和治疗细菌感染，特别是由大肠杆菌引起的泌尿系统感染、 其中 R1 为以下 (B)、(C)、(D)、(E) 组之一：
• [EN] MANNOSE DERIVATIVES AS ANTAGONISTS OF BACTERIAL ADHESION<br/>[FR] DÉRIVÉS DE MANNOSE UTILISÉS EN TANT QU'ANTAGONISTES DE L'ADHÉSION BACTÉRIENNE
  申请人：UNIV BASEL

  公开号：WO2011073112A3

  公开（公告）日：2011-09-09
• 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.