α-D-manno-non-pyranoside, ethyl-6,7,8,9-tetradeoxy-2-O-benzyl-3,4-di-O-methyl-1-thio | 647030-10-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: α-D-manno-non-pyranoside, ethyl-6,7,8,9-tetradeoxy-2-O-benzyl-3,4-di-O-methyl-1-thio
• 英文别名: (2R,3S,4S,5R,6R)-2-ethylsulfanyl-4,5-dimethoxy-6-(3-methylbutyl)-3-phenylmethoxyoxane
• CAS: 647030-10-2
• 化学式: C₂₁H₃₄O₄S
• 分子量: 382.565
• InChiKey: SBZMTHXAMBTMFU-CRSSMBPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  62.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  α-D-manno-non-pyranoside, ethyl-6,7,8,9-tetradeoxy-2-O-benzyl-3,4-di-O-methyl-1-thio 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 (3S,4S,5R,6R)-3-Benzyloxy-4,5-dimethoxy-6-(3-methyl-butyl)-tetrahydro-pyran-2-ol
  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：

  (2R,3S,4S,5S,6R)-5-Benzyloxy-6-ethylsulfanyl-2-(3-methyl-butyl)-tetrahydro-pyran-3,4-diol 、 碘甲烷 在 氢氧化钾 作用下， 以 二甲基亚砜 为溶剂， 以90%的产率得到α-D-manno-non-pyranoside, ethyl-6,7,8,9-tetradeoxy-2-O-benzyl-3,4-di-O-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