methyl 2,3,4-tri-O-acetyl-6-sulfamoyl-α-D-glucopyranose | 1268376-49-3

• 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-sulfamoyl-α-D-glucopyranose
• 英文别名: Methyl 2,3,4-Tri-O-acetyl-6-sulfamoyl-alpha-D-glucopyranose；[(2R,3R,4S,5R,6S)-4,5-diacetyloxy-6-methoxy-2-(sulfamoyloxymethyl)oxan-3-yl] acetate
• CAS: 1268376-49-3
• 化学式: C₁₃H₂₁NO₁₁S
• 分子量: 399.376
• InChiKey: JMWXVVGVHXWFKB-LBELIVKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  175
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  methyl 2,3,4-tri-O-acetyl-6-sulfamoyl-α-D-glucopyranose 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以94%的产率得到((2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-methoxytetrahydro-2H-pyran-2-yl)methyl sulfamate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Carbohydrate-Based Sulfamates as Carbonic Anhydrase Inhibitors

  摘要：

  Carbonic anhydrases (CAs) IX and XII are enzymes with newly validated potential for the development of personalized, first-in-class cancer chemotherapies. Here we present the design and synthesis of novel carbohydrate-based CA inhibitors, several of which were very efficient inhibitors (K-i < 10 nM) with good selectivity for cancer-associated CA isozymes over off-target CA isozymes. All inhibitors comprised a carbohydrate core with one hydroxyl group derivatized as a sulfamate. Five different carbohydrates were chosen to present a selection of molecular shapes with subtle stereochernical differences to the CA enzymes active site. Variable modifications of the remaining sugar hydroxyl groups were incorporated to provide an incremental coverage of chemical property parameters that are associated with biopharmaceutical performance. All sulfamate inhibitors displayed ligand efficiencies that are consistent with those reported for good drug lead candidates.

  DOI：

  10.1021/jm101525j
• 作为产物：
  描述：

  methyl 2,3,4-tri-O-acetyl-α-D-glucopyranose 在 氨基磺酰氯 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 以61%的产率得到methyl 2,3,4-tri-O-acetyl-6-sulfamoyl-α-D-glucopyranose
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Carbohydrate-Based Sulfamates as Carbonic Anhydrase Inhibitors

  摘要：

  Carbonic anhydrases (CAs) IX and XII are enzymes with newly validated potential for the development of personalized, first-in-class cancer chemotherapies. Here we present the design and synthesis of novel carbohydrate-based CA inhibitors, several of which were very efficient inhibitors (K-i < 10 nM) with good selectivity for cancer-associated CA isozymes over off-target CA isozymes. All inhibitors comprised a carbohydrate core with one hydroxyl group derivatized as a sulfamate. Five different carbohydrates were chosen to present a selection of molecular shapes with subtle stereochernical differences to the CA enzymes active site. Variable modifications of the remaining sugar hydroxyl groups were incorporated to provide an incremental coverage of chemical property parameters that are associated with biopharmaceutical performance. All sulfamate inhibitors displayed ligand efficiencies that are consistent with those reported for good drug lead candidates.

  DOI：

  10.1021/jm101525j

文献信息

• Design, Synthesis, and Biological Evaluation of Novel Carbohydrate-Based Sulfamates as Carbonic Anhydrase Inhibitors
  作者：Marie Lopez、Jonathan Trajkovic、Laurent F. Bornaghi、Alessio Innocenti、Daniela Vullo、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1021/jm101525j

  日期：2011.3.10

  Carbonic anhydrases (CAs) IX and XII are enzymes with newly validated potential for the development of personalized, first-in-class cancer chemotherapies. Here we present the design and synthesis of novel carbohydrate-based CA inhibitors, several of which were very efficient inhibitors (K-i < 10 nM) with good selectivity for cancer-associated CA isozymes over off-target CA isozymes. All inhibitors comprised a carbohydrate core with one hydroxyl group derivatized as a sulfamate. Five different carbohydrates were chosen to present a selection of molecular shapes with subtle stereochernical differences to the CA enzymes active site. Variable modifications of the remaining sugar hydroxyl groups were incorporated to provide an incremental coverage of chemical property parameters that are associated with biopharmaceutical performance. All sulfamate inhibitors displayed ligand efficiencies that are consistent with those reported for good drug lead candidates.