4-[4-(aminosulfonyl)phenyl]-1-(2'-acetamido-2'-deoxy-β-D-glucopyranosyl)-1H-1,2,3-triazole | 1017276-64-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[4-(aminosulfonyl)phenyl]-1-(2'-acetamido-2'-deoxy-β-D-glucopyranosyl)-1H-1,2,3-triazole
• 英文别名: N-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-[4-(4-sulfamoylphenyl)triazol-1-yl]oxan-3-yl]acetamide
• CAS: 1017276-64-0
• 化学式: C₁₆H₂₁N₅O₇S
• 分子量: 427.438
• InChiKey: WRBIMYXSAKHNPY-OXGONZEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  198
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-[4-(aminosulfonyl)phenyl]-1-(2'-acetamido-2'-deoxy-3',4',6'-tri-O-acetyl-β-D-glucopyranosyl)-1H-1,2,3-triazole 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以116 mg的产率得到4-[4-(aminosulfonyl)phenyl]-1-(2'-acetamido-2'-deoxy-β-D-glucopyranosyl)-1H-1,2,3-triazole
  参考文献：
  名称：

  Inhibition of Carbonic Anhydrases with Glycosyltriazole Benzene Sulfonamides

  摘要：

  library of glycoconjugate benzene sulfonamides have been synthesized and investigated for their ability to inhibit the enzymatic activity of physiologically relevant human carbonic anhydrase (hCA) isozymes: hCA I, II, and tumor-associated IX. Our synthetic strategy directly links the known CA pharmacophore (ArSO2NH2) to a sugar "tail" moiety through a rigid 1,2,3-triazole linker unit using the Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction or "click chemistry". Many of the glycoconjugates were potent CA inhibitors and exhibited some isozyme selectivity. In particular, the methyl-D-glucuronate triazoles 6 and 14 were potent inhibitors of hCA IX (K(i)s 9.9 and 8.4 nM, respectively) with selectivity also favoring this isozyme. Other exceptional compounds included the deprotected beta-D-ribofuranosyl triazole 15 and alpha-D-mannosyl triazole 17, which were potent and selective hCA II inhibitors (K-i 7.5 nM and K-i 2.3 nM, respectively). Collectively, the results confirm that modification of ring size, stereochemical configuration, and chain length in the sugar tail moiety of glycoconjugate CA inhibitors permits tunable potency and selectivity that may constitute an important avenue for the future development of efficacious and selective CA-based therapeutics.

  DOI：

  10.1021/jm701426t

文献信息

• Inhibition of Carbonic Anhydrases with Glycosyltriazole Benzene Sulfonamides
  作者：Brendan L. Wilkinson、Alessio Innocenti、Daniela Vullo、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1021/jm701426t

  日期：2008.3.1

  library of glycoconjugate benzene sulfonamides have been synthesized and investigated for their ability to inhibit the enzymatic activity of physiologically relevant human carbonic anhydrase (hCA) isozymes: hCA I, II, and tumor-associated IX. Our synthetic strategy directly links the known CA pharmacophore (ArSO2NH2) to a sugar "tail" moiety through a rigid 1,2,3-triazole linker unit using the Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction or "click chemistry". Many of the glycoconjugates were potent CA inhibitors and exhibited some isozyme selectivity. In particular, the methyl-D-glucuronate triazoles 6 and 14 were potent inhibitors of hCA IX (K(i)s 9.9 and 8.4 nM, respectively) with selectivity also favoring this isozyme. Other exceptional compounds included the deprotected beta-D-ribofuranosyl triazole 15 and alpha-D-mannosyl triazole 17, which were potent and selective hCA II inhibitors (K-i 7.5 nM and K-i 2.3 nM, respectively). Collectively, the results confirm that modification of ring size, stereochemical configuration, and chain length in the sugar tail moiety of glycoconjugate CA inhibitors permits tunable potency and selectivity that may constitute an important avenue for the future development of efficacious and selective CA-based therapeutics.