2-chloro-4-iodophenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside | 1312312-40-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-iodophenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside
• 英文别名: 2-Chloro-4-iodophenyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranoside；[(2R,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-(2-chloro-4-iodophenoxy)oxan-2-yl]methyl acetate
• CAS: 1312312-40-5
• 化学式: C₂₀H₂₂ClIO₁₀
• 分子量: 584.746
• InChiKey: XWQYJENBAFIJPF-SLHNCBLASA-N

物化性质

• 沸点：
  563.5±50.0 °C(Predicted)
• 密度：
  1.63±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  2-chloro-4-iodophenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside 在 potassium phosphate 、 trans cyclohexane-1,2-diamine 、 sodium methylate 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 methyl 1-(3-chloro-4-(α-D-mannopyranosyloxy)phenyl)-1H-indole-5-carboxylate
  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-氯-4-碘苯酚 、 1,2,3,4,6-O-五乙酰基-Alpha-甘露糖 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以76%的产率得到2-chloro-4-iodophenyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranoside
  参考文献：
  名称：

  尿路感染：细菌凝集素FimH的哪些构型在治疗上相关？

  摘要：

  尿道感染的频繁抗生素治疗导致出现了抗药性，因此需要其他治疗选择。一种这样的方法围绕着FimH拮抗剂，该拮抗剂阻断细菌粘附素FimH，否则会介导尿毒原性大肠杆菌的结合到宿主尿路上皮触发感染。尽管FimH凝集素可以采用三种不同的构象，但FimH拮抗剂的评估主要是通过将FimH的截短构建体锁定在一个特定构象中来进行的。但是，对于成功的治疗应用，FimH拮抗剂应对所有生理相关构象有效。因此，使用了具有采取各种构象能力的FimH构建体。通过检查一系列FimH拮抗剂在结合亲和力和热力学方面的结合特性，我们证明了根据FimH构建体，亲和力可能被2个数量级的常数因子高估。此外，我们报告了几种对所有FimH构象都具有出色亲和力的拮抗剂。

  DOI：

  10.1021/acs.jmedchem.7b00342

文献信息

• [EN] MANNOSE PHOSPHATE DERIVATIVES AS ANTAGONISTS OF BACTERIAL ADHESION<br/>[FR] DÉRIVÉS DE MANNOSE PHOSPHATE EN TANT QU'ANTAGONISTES DE L'ADHÉSION BACTÉRIENNE
  申请人：UNIV BASEL

  公开号：WO2012164074A1

  公开（公告）日：2012-12-06

  Compounds of the formula (I) (I) wherein n is 0, 1 or 2, R1 is aryl, heteroaryl or heterocyclyl, and R2 and R3 are, independent of each other, hydrogen or a substituent as described in the specification, and one of RA, RB, RC and RD is P02(OH)2 and the other ones are hydrogen; are orally available medicaments useful for the prevention and treatment of bacterial infections, in particular of urinary infections caused by E. coli.

  公式(I)（I）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独立地为氢或如说明书中所描述的取代基，且RA、RB、RC和RD中的一个为P02(OH)2，其余为氢；是口服可用的药物，用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。
• Improvement of Aglycone π‐Stacking Yields Nanomolar to Sub‐nanomolar FimH Antagonists
  作者：Wojciech Schönemann、Jonathan Cramer、Tobias Mühlethaler、Brigitte Fiege、Marleen Silbermann、Said Rabbani、Philipp Dätwyler、Pascal Zihlmann、Roman P. Jakob、Christoph P. Sager、Martin Smieško、Oliver Schwardt、Timm Maier、Beat Ernst

  DOI：10.1002/cmdc.201900051

  日期：2019.4.3

  demonstrate that fluorination of biphenyl α-d-mannosides leads to compounds with perfect π-π stacking interactions with the tyrosine gate of FimH, yielding low nanomolar to sub-nanomolar KD values for the low- and high-affinity states, respectively. The face-to-face alignment of the perfluorinated biphenyl group of FimH ligands and Tyr48 was confirmed by crystal structures as well as 1 H,15 N-HSQC NMR analysis

  抗菌素耐药性已成为治疗尿路感染的严重问题。在这种情况下，针对FimH（一种细菌凝集素，能够将大肠杆菌附着到宿主细胞上）的抗粘连方法引起了极大的兴趣。FimH可以在不存在剪切力的情况下采用低/中亲和力状态，而在存在剪切力的情况下可以采用高亲和力状态。直到最近，尽管治疗性拮抗剂应主要结合至低亲和力状态，但大多数情况下仍对高亲和力状态进行了研究。在本交流中，我们证明了联苯α-d-甘露糖苷的氟化作用导致与FimH的酪氨酸门具有完美的π-π堆积相互作用的化合物，从而产生低纳摩尔至亚纳摩尔级的KD值，用于低亲和力和高亲和力状态， 分别。FimH配体和Tyr48的全氟化联苯的面对面排列通过晶体结构以及1 H，15 N-HSQC NMR分析确认。最后，氟化改善了预测口服有效性的药代动力学参数。
• 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：