(8bS,9aR,10R,13S,13aR,14aS)-12-[2-(tert-Butyl-diphenyl-silanyloxy)-ethoxy]-10-isobutoxymethyl-8b,14a-dimethoxy-8b,9a,12,13,13a,14a-hexahydro-10H-9,11,14-trioxa-benzo[b]triphenylen-13-ol | 647029-91-2

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (8bS,9aR,10R,13S,13aR,14aS)-12-[2-(tert-Butyl-diphenyl-silanyloxy)-ethoxy]-10-isobutoxymethyl-8b,14a-dimethoxy-8b,9a,12,13,13a,14a-hexahydro-10H-9,11,14-trioxa-benzo[b]triphenylen-13-ol
• CAS: 647029-91-2
• 化学式: C₄₄H₅₄O₉Si
• 分子量: 754.993
• InChiKey: OOPSZMXXBGTQRZ-YHOUQYBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  54.0
• 可旋转键数：
  13.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  94.07
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (8bS,9aR,10R,13S,13aR,14aS)-12-[2-(tert-Butyl-diphenyl-silanyloxy)-ethoxy]-10-isobutoxymethyl-8b,14a-dimethoxy-8b,9a,12,13,13a,14a-hexahydro-10H-9,11,14-trioxa-benzo[b]triphenylen-13-ol 在 palladium on activated charcoal 氢氧化钾 、 sodium chlorite 、 disodium hydrogenphosphate 、 四丁基氟化铵 、 氢气 、 三氧化硫吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 叔丁醇 为溶剂， 反应 4.5h， 生成 [carboxylmethyl]-2-O-[2'-hydroxyethyl]-3,4-O-[9',10'-dimethoxyphenanthrene-9',10'-diyl]-6-O-isobutyl-α-D-mannopyranoside
  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：

  [2-((8bS,9aS,10S,13R,13aR,14aS)-10-Benzyloxy-13-isobutoxymethyl-8b,14a-dimethoxy-8b,10,11,13,13a,14a-hexahydro-9aH-9,12,14-trioxa-benzo[b]triphenylen-11-yloxy)-ethoxy]-tert-butyl-diphenyl-silane 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 (8bS,9aR,10R,13S,13aR,14aS)-12-[2-(tert-Butyl-diphenyl-silanyloxy)-ethoxy]-10-isobutoxymethyl-8b,14a-dimethoxy-8b,9a,12,13,13a,14a-hexahydro-10H-9,11,14-trioxa-benzo[b]triphenylen-13-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