N-2′-sulfamoylethyl-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranosyl)sulfonamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-2′-sulfamoylethyl-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranosyl)sulfonamide
• 英文别名: [(2R,3R,4S,5R,6S)-3,4,5-triacetyloxy-6-(2-sulfamoyloxyethylsulfamoyl)oxan-2-yl]methyl acetate
• 化学式: C₁₆H₂₆N₂O₁₄S₂
• 分子量: 534.519
• InChiKey: XWGMBFCMKKHXPR-LJIZCISZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  247
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  N-2′-sulfamoylethyl-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranosyl)sulfonamide 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Structural Insights into Carbonic Anhydrase IX Isoform Specificity of Carbohydrate-Based Sulfamates

  摘要：

  Carbonic anhydrase IX (CA IX) is an extracellular transmembrane homodimeric zinc metalloenzyme that has been validated as a prognostic marker and therapeutic target for several types of aggressive cancers. CA IX shares a close homology with other CA isoforms, making the design of CA IX isoform selective inhibitors challenging. In this paper, we describe the development of a new class of CA IX inhibitors that comprise a sulfamate as the zinc binding group, a variable linker, and a carbohydrate "tail" moiety. Seven compounds inhibited CA IX with low nM Ki values of 1-2 nM and also exhibited permeability profiles to preferentially target the binding of extracellular CA IX over cytosolic CAs. The crystal structures of two of these compounds in complex with a CA IX-mimic (a variant of CA II, with active site residues that mimic CA IX) and one compound in complex with CA II have been determined to 1.7 angstrom resolution or better and demonstrate a selective mechanism of binding between the hydrophilic and hydrophobic pockets of CA IX versus CA II. These compounds present promising candidates for anti-CA IX drugs and the treatment for several aggressive cancer types.

  DOI：

  10.1021/jm5012935
• 作为产物：
  描述：

  1-硫代-beta-D-葡萄糖五乙酸酯 在 氨基磺酰氯 、 溴代丙二酸二乙酯 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.33h， 生成 N-2′-sulfamoylethyl-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranosyl)sulfonamide
  参考文献：
  名称：

  Structural Insights into Carbonic Anhydrase IX Isoform Specificity of Carbohydrate-Based Sulfamates

  摘要：

  Carbonic anhydrase IX (CA IX) is an extracellular transmembrane homodimeric zinc metalloenzyme that has been validated as a prognostic marker and therapeutic target for several types of aggressive cancers. CA IX shares a close homology with other CA isoforms, making the design of CA IX isoform selective inhibitors challenging. In this paper, we describe the development of a new class of CA IX inhibitors that comprise a sulfamate as the zinc binding group, a variable linker, and a carbohydrate "tail" moiety. Seven compounds inhibited CA IX with low nM Ki values of 1-2 nM and also exhibited permeability profiles to preferentially target the binding of extracellular CA IX over cytosolic CAs. The crystal structures of two of these compounds in complex with a CA IX-mimic (a variant of CA II, with active site residues that mimic CA IX) and one compound in complex with CA II have been determined to 1.7 angstrom resolution or better and demonstrate a selective mechanism of binding between the hydrophilic and hydrophobic pockets of CA IX versus CA II. These compounds present promising candidates for anti-CA IX drugs and the treatment for several aggressive cancer types.

  DOI：

  10.1021/jm5012935

文献信息

• Structural Insights into Carbonic Anhydrase IX Isoform Specificity of Carbohydrate-Based Sulfamates
  作者：Janina Moeker、Brian P. Mahon、Laurent F. Bornaghi、Daniela Vullo、Claudiu T. Supuran、Robert McKenna、Sally-Ann Poulsen

  DOI：10.1021/jm5012935

  日期：2014.10.23

  Carbonic anhydrase IX (CA IX) is an extracellular transmembrane homodimeric zinc metalloenzyme that has been validated as a prognostic marker and therapeutic target for several types of aggressive cancers. CA IX shares a close homology with other CA isoforms, making the design of CA IX isoform selective inhibitors challenging. In this paper, we describe the development of a new class of CA IX inhibitors that comprise a sulfamate as the zinc binding group, a variable linker, and a carbohydrate "tail" moiety. Seven compounds inhibited CA IX with low nM Ki values of 1-2 nM and also exhibited permeability profiles to preferentially target the binding of extracellular CA IX over cytosolic CAs. The crystal structures of two of these compounds in complex with a CA IX-mimic (a variant of CA II, with active site residues that mimic CA IX) and one compound in complex with CA II have been determined to 1.7 angstrom resolution or better and demonstrate a selective mechanism of binding between the hydrophilic and hydrophobic pockets of CA IX versus CA II. These compounds present promising candidates for anti-CA IX drugs and the treatment for several aggressive cancer types.