methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-β-D-glucopyranoside | 888936-32-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-β-D-glucopyranoside
• 英文别名: [(2R,3R,4S,5R,6R)-4,5-diacetyloxy-2-(aminomethyl)-6-methoxyoxan-3-yl] acetate
• CAS: 888936-32-1
• 化学式: C₁₃H₂₁NO₈
• 分子量: 319.312
• InChiKey: VYDBDCQBZQQWCJ-UJPOAAIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-β-D-glucopyranoside 在 甲醇 、 氨 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (2R)-3-methyl-2-(N-(2-(3-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-methoxytetrahydro-2H-pyran-2-yl)methyl)thioureido)ethyl)biphenyl-4-ylsulfonamido)butanoic acid
  参考文献：
  名称：

  Matrix metalloproteinase-12 inhibitors: synthesis, structure-activity relationships and intestinal absorption of novel sugar-based biphenylsulfonamide carboxylates

  摘要：

  MMP-12 is a validated target in pulmonary and cardiovascular diseases. The principal obstacles to clinical development of MMP-12 inhibitors are an inadequate selectivity for the target enzyme and a poor water solubility, with consequent poor oral bioavailability. We recently reported a new class of sugar-based arylsulfonamide carboxylates with a nanomolar activity for MMP-12, a good selectivity and an improved water solubility. In this study, we designed and synthesized new derivatives to characterize the structure-activity relationship (SAR) within this class of glycoconjugate inhibitors. All the new derivatives were tested on human recombinant MMP-12 and MMP-9 in order to evaluate their affinity and the selectivity for the target enzyme. Among them, the four most promising compounds were selected to assess their intestinal permeability using an ex vivo everted gut sac model. Given the high polarity and structural similarity to glucose, compound 3 was demonstrated to cross the intestinal membrane by using the facilitative GLUT2 transport.

  DOI：

  10.1016/j.bmc.2018.10.024
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  Matrix metalloproteinase-12 inhibitors: synthesis, structure-activity relationships and intestinal absorption of novel sugar-based biphenylsulfonamide carboxylates

  摘要：

  MMP-12 is a validated target in pulmonary and cardiovascular diseases. The principal obstacles to clinical development of MMP-12 inhibitors are an inadequate selectivity for the target enzyme and a poor water solubility, with consequent poor oral bioavailability. We recently reported a new class of sugar-based arylsulfonamide carboxylates with a nanomolar activity for MMP-12, a good selectivity and an improved water solubility. In this study, we designed and synthesized new derivatives to characterize the structure-activity relationship (SAR) within this class of glycoconjugate inhibitors. All the new derivatives were tested on human recombinant MMP-12 and MMP-9 in order to evaluate their affinity and the selectivity for the target enzyme. Among them, the four most promising compounds were selected to assess their intestinal permeability using an ex vivo everted gut sac model. Given the high polarity and structural similarity to glucose, compound 3 was demonstrated to cross the intestinal membrane by using the facilitative GLUT2 transport.

  DOI：

  10.1016/j.bmc.2018.10.024

文献信息

• Prabhu, Girish; Sureshbabu, Vommina V, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 4, p. 526 - 534
  作者：Prabhu, Girish、Sureshbabu, Vommina V

  DOI：——

  日期：——