(1S,3S,4S,6R,7S,8S,10S)-6-ethylsulfanyl-1,10-dimethoxy-7-phenylmethoxy-2,5,9-trioxatricyclo[8.4.0.03,8]tetradecane-4-carbaldehyde | 1054624-09-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1S,3S,4S,6R,7S,8S,10S)-6-ethylsulfanyl-1,10-dimethoxy-7-phenylmethoxy-2,5,9-trioxatricyclo[8.4.0.03,8]tetradecane-4-carbaldehyde
• CAS: 1054624-09-7
• 化学式: C₂₃H₃₂O₇S
• 分子量: 452.569
• InChiKey: NCQMECBFYNWUSK-NUNPFQGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  97.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1S,3S,4S,6R,7S,8S,10S)-6-ethylsulfanyl-1,10-dimethoxy-7-phenylmethoxy-2,5,9-trioxatricyclo[8.4.0.03,8]tetradecane-4-carbaldehyde 在 palladium on activated charcoal 氢气 、 双(三甲基硅烷基)氨基钾 、 乙二胺 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， -10.0~20.0 ℃ 、5.0 kPa 条件下， 反应 15.5h， 生成 (1R,3R,4S,4aS,8aS,9aR,10aS)-4-Benzyloxy-3-ethylsulfanyl-1-isobutyl-8a,10a-dimethoxy-decahydro-2,9,10-trioxa-anthracene
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Mannose-Based Peptidomimetics Selectively Blocking Integrin α4β7 Binding to Mucosal Addressin Cell Adhesion Molecule-1

  摘要：

  As part of our ongoing research in the development of alpha4beta7 integrin antagonists, we are interested in peptidomimetics based on a rigid scaffold to allow the display of essential side chains in a suitable binding conformation while eliminating backbone amide bonds and therefore improving pharmacokinetic parameters of the drug. Except for a few examples, peptidomimetics scaffolds have only been moderately successful and often yield molecules that lack the potency of their peptide counterparts. However, we present herein a successful application of using a rigid scaffold. Starting from a mannopyranoside analogue previously discovered in our laboratory as an inhibitor of the alpha4beta1/vascular cell adhesion molecule interaction, a biased library of functionalized carbohydrates was developed. One compound emerged from this library as an active and selective antagonist toward the alpha4beta7/mucosal addressin cell adhesion molecule interaction. Conformational. implications and the relevance of different pharmacophoric patterns will be discussed in order to explain the reverse selectivity and enhanced affinity.

  DOI：

  10.1021/jm020487h
• 作为产物：
  描述：

  (1'S,2'S)-Ethyl 3,4-O-(1',2'-dimethoxycyclohexane-1',2'-diyl)-1-thio-α-D-mannopyranoside 在 氢氧化钾 、 三氧化硫吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 0.5h， 生成 (1S,3S,4S,6R,7S,8S,10S)-6-ethylsulfanyl-1,10-dimethoxy-7-phenylmethoxy-2,5,9-trioxatricyclo[8.4.0.03,8]tetradecane-4-carbaldehyde
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Mannose-Based Peptidomimetics Selectively Blocking Integrin α4β7 Binding to Mucosal Addressin Cell Adhesion Molecule-1

  摘要：

  As part of our ongoing research in the development of alpha4beta7 integrin antagonists, we are interested in peptidomimetics based on a rigid scaffold to allow the display of essential side chains in a suitable binding conformation while eliminating backbone amide bonds and therefore improving pharmacokinetic parameters of the drug. Except for a few examples, peptidomimetics scaffolds have only been moderately successful and often yield molecules that lack the potency of their peptide counterparts. However, we present herein a successful application of using a rigid scaffold. Starting from a mannopyranoside analogue previously discovered in our laboratory as an inhibitor of the alpha4beta1/vascular cell adhesion molecule interaction, a biased library of functionalized carbohydrates was developed. One compound emerged from this library as an active and selective antagonist toward the alpha4beta7/mucosal addressin cell adhesion molecule interaction. Conformational. implications and the relevance of different pharmacophoric patterns will be discussed in order to explain the reverse selectivity and enhanced affinity.

  DOI：

  10.1021/jm020487h

文献信息

• Synthesis and Structure−Activity Relationship of Mannose-Based Peptidomimetics Selectively Blocking Integrin α4β7 Binding to Mucosal Addressin Cell Adhesion Molecule-1
  作者：Elsa Locardi、Jürgen Boer、Armin Modlinger、Anja Schuster、Bernhard Holzmann、Horst Kessler

  DOI：10.1021/jm020487h

  日期：2003.12.1

  As part of our ongoing research in the development of alpha4beta7 integrin antagonists, we are interested in peptidomimetics based on a rigid scaffold to allow the display of essential side chains in a suitable binding conformation while eliminating backbone amide bonds and therefore improving pharmacokinetic parameters of the drug. Except for a few examples, peptidomimetics scaffolds have only been moderately successful and often yield molecules that lack the potency of their peptide counterparts. However, we present herein a successful application of using a rigid scaffold. Starting from a mannopyranoside analogue previously discovered in our laboratory as an inhibitor of the alpha4beta1/vascular cell adhesion molecule interaction, a biased library of functionalized carbohydrates was developed. One compound emerged from this library as an active and selective antagonist toward the alpha4beta7/mucosal addressin cell adhesion molecule interaction. Conformational. implications and the relevance of different pharmacophoric patterns will be discussed in order to explain the reverse selectivity and enhanced affinity.