α-D-manno-oct-6-enopyranoside, ethyl-6,7,8-trideoxy-2-O-benzyl-3,4-O-[1',2'-dimethoxycyclohexan-1',2'-diyl]-7-methyl-1-thio | 647030-05-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: α-D-manno-oct-6-enopyranoside, ethyl-6,7,8-trideoxy-2-O-benzyl-3,4-O-[1',2'-dimethoxycyclohexan-1',2'-diyl]-7-methyl-1-thio
• 英文别名: (1S,3R,4R,6R,7S,8S,10S)-6-ethylsulfanyl-1,10-dimethoxy-4-(2-methylprop-1-enyl)-7-phenylmethoxy-2,5,9-trioxatricyclo[8.4.0.03,8]tetradecane
• CAS: 647030-05-5
• 化学式: C₂₆H₃₈O₆S
• 分子量: 478.65
• InChiKey: KOUDDYSHIVDYNW-NYMVXWMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  80.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  α-D-manno-oct-6-enopyranoside, ethyl-6,7,8-trideoxy-2-O-benzyl-3,4-O-[1',2'-dimethoxycyclohexan-1',2'-diyl]-7-methyl-1-thio 在 palladium on activated charcoal 氢气 、 乙二胺 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、5.0 kPa 条件下， 反应 12.0h， 以80%的产率得到(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 、 双(三甲基硅烷基)氨基钾 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 4.0h， 生成 α-D-manno-oct-6-enopyranoside, ethyl-6,7,8-trideoxy-2-O-benzyl-3,4-O-[1',2'-dimethoxycyclohexan-1',2'-diyl]-7-methyl-1-thio
  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.