4-(5-nitroindolin-1-yl)phenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside | 1312312-41-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(5-nitroindolin-1-yl)phenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside
• 英文别名: 4-(5-Nitroindolin-1-yl)phenyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranoside；[(2R,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-[4-(5-nitro-2,3-dihydroindol-1-yl)phenoxy]oxan-2-yl]methyl acetate
• CAS: 1312312-41-6
• 化学式: C₂₈H₃₀N₂O₁₂
• 分子量: 586.552
• InChiKey: VOXQEBQJUNIKOS-MASCHLQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  173
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  4-(5-nitroindolin-1-yl)phenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside 在 甲醇 、 sodium methylate 作用下， 反应 20.0h， 以50%的产率得到4-(5-nitroindolin-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：

  2,3,4,6-四-O-乙酰基吡喃己糖 在 tris-(dibenzylideneacetone)dipalladium(0) 三氟甲磺酸三甲基硅酯 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 146.0h， 生成 4-(5-nitroindolin-1-yl)phenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside
  参考文献：
  名称：

  [EN] MANNOSE DERIVATIVES AS ANTAGONISTS OF BACTERIAL ADHESION
  [FR] DÉRIVÉS DE MANNOSE UTILISÉS EN TANT QU'ANTAGONISTES DE L'ADHÉSION BACTÉRIENNE

  摘要：

  公开号：

  WO2011073112A3

文献信息

• Kinetic Properties of Carbohydrate-Lectin Interactions: FimH Antagonists
  作者：Meike Scharenberg、Xiaohua Jiang、Lijuan Pang、Giulio Navarra、Said Rabbani、Florian Binder、Oliver Schwardt、Beat Ernst

  DOI：10.1002/cmdc.201300349

  日期：2014.1

  part of the preclinical development process, when the kinetic properties of FimH antagonists were examined by surface plasmon resonance, extremely low dissociation rates (koff) were found, which is uncommon for carbohydrate–lectin interactions. As a consequence, the corresponding half‐lives (t1/2) of the FimH antagonist complexes are above 3.6 h. For a therapeutic application, extended t1/2 values are

  凝集素FimH在尿路致病性大肠杆菌（UPEC）的1型菌毛上最终表达，这是尿路感染（UTI）的主要原因。FimH使细菌粘附到尿道上皮细胞，这是感染的第一步。各种甘露糖衍生物已显示出拮抗FimH，因此被认为是用于治疗UTI的有前途的治疗剂。作为临床前开发过程的一部分，当通过表面等离子体激元共振检查FimH拮抗剂的动力学特性时，发现极低的解离速率（k off），这在碳水化合物-凝集素相互作用中并不常见。结果，相应的半衰期（t 1/2）的FimH拮抗剂复合物在3.6 h以上。对于治疗应用而言，扩展的t 1/2值是成功的先决条件，因为目标占用时间直接影响体内药物的功效。经过测试的FimH拮抗剂的t 1/2值长，进一步证实了它们的药物样特性和高治疗潜力。
• 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：