4-{4-[(2’,3’,4’,6’-tetra-O-acetyl-β-D-galactopyranosyl)oxymethyl]-1H-1,2,3-triazol-1-yl}benzenesulfonamide | 935678-25-4

• 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: 4-{4-[(2’,3’,4’,6’-tetra-O-acetyl-β-D-galactopyranosyl)oxymethyl]-1H-1,2,3-triazol-1-yl}benzenesulfonamide
• 英文别名: 4-(4-{(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)oxymethyl}-1-H-1,2,3-triazol-1-yl)benzenesulfonamide；[(2R,3S,4S,5R,6R)-3,4,5-tris(acetyloxy)-6-{[1-(4-sulfamoylphenyl)-1H-1,2,3-triazol-4-yl]methoxy}oxan-2-yl]methyl acetate；[(2R,3S,4S,5R,6R)-3,4,5-triacetyloxy-6-[[1-(4-sulfamoylphenyl)triazol-4-yl]methoxy]oxan-2-yl]methyl acetate
• CAS: 935678-25-4
• 化学式: C₂₃H₂₈N₄O₁₂S
• 分子量: 584.561
• InChiKey: QGAJDSWCAJPCOD-BMXMUORJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  40
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  223
• 氢给体数：
  1
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  4-{4-[(2’,3’,4’,6’-tetra-O-acetyl-β-D-galactopyranosyl)oxymethyl]-1H-1,2,3-triazol-1-yl}benzenesulfonamide 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以100%的产率得到4-(4-{(β-D-galactopyranosyl)oxymethyl}-1-H-1,2,3-triazol-1-yl)benzenesulfonamide
  参考文献：
  名称：

  Carbonic Anhydrase Inhibitors:  Inhibition of Isozymes I, II, and IX with Triazole-Linked O-Glycosides of Benzene Sulfonamides

  摘要：

  We report the synthesis of a series of benzene sulfonamides containing triazole-O-glycoside tails for evaluation as carbonic anhydrase (CA) inhibitors. These glycoconjugates were synthesized by the 1,3-dipolar cycloaddition reaction of 4-azidobenzenesulfonamide with O-propynyl glycosides. Compounds were assessed for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA I and II and the tumor-associated isozyme hCA IX (h = human). Against hCA I these compounds were either micromolar or low-nanomolar inhibitors, while against hCA II and IX inhibition in the range of 6.8-53 and 9.7-107 nM, respectively, was observed. The most potent inhibitor against hCA IX was the galactose derivative 8 (K-i = 9.7 nM); this is so far the most potent glycoconjugate inhibitor reported for the tumor-associated hCA IX. These carbohydrate-tethered sulfonamides may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly.

  DOI：

  10.1021/jm061320h
• 作为产物：
  描述：

  磺胺 在 sodium azide 、 亚硝酸特丁酯 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 1.25h， 生成 4-{4-[(2’,3’,4’,6’-tetra-O-acetyl-β-D-galactopyranosyl)oxymethyl]-1H-1,2,3-triazol-1-yl}benzenesulfonamide
  参考文献：
  名称：

  Synthesis andin vitroEvaluation of Novel Galactosyl-triazolo-benzenesulfonamides AgainstTrypanosoma cruzi

  摘要：

  The only drugs approved for the treatment of Chagas disease, nifurtimox and benznidazole, present toxic side effects and limited efficacy in the chronic stage of the disease, which highlight the need for new drugs. Amongst the different molecular drug targets discovered in the parasite, Trypanosoma cruzi trans-sialidase (TcTS) has been considered crucial in the recognition and invasion of host cells. Hence, we report the efficient synthesis and biological evaluation (TcTS inhibition and antitrypanosomal activities) of some galactose-containing triazol-arylsulfonamides via microwave-assisted Cu(I) 1,3-dipolar azide-alkyne cycloaddition (CuAAC) based on azide benzenesulfonamides and a galactose-derived alkyne as precursors. Most of the compounds tested against TcTS showed moderate to weak inhibition (40%-15%), except one of the compounds (81%). Regarding the antitrypanosomal assay, some compounds [(IC50 70.9 mu M) and (IC50 44.0 mu M)] exhibited the most significant activities, although not as active as benznidazole (IC50 1.4 mu M). Nevertheless, the cytotoxicity assessment showed that all compounds were not cytotoxic. In this preliminary work, we considered some compounds as lead scaffolds for further optimization.

  DOI：

  10.5935/0103-5053.20140158

文献信息

• Carbonic Anhydrase Inhibitors:  Inhibition of Isozymes I, II, and IX with Triazole-Linked <i>O</i>-Glycosides of Benzene Sulfonamides
  作者：Brendan L. Wilkinson、Laurent F. Bornaghi、Todd A. Houston、Alessio Innocenti、Daniela Vullo、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1021/jm061320h

  日期：2007.4.1

  We report the synthesis of a series of benzene sulfonamides containing triazole-O-glycoside tails for evaluation as carbonic anhydrase (CA) inhibitors. These glycoconjugates were synthesized by the 1,3-dipolar cycloaddition reaction of 4-azidobenzenesulfonamide with O-propynyl glycosides. Compounds were assessed for their ability to inhibit the enzymatic activity of the physiologically dominant isozymes hCA I and II and the tumor-associated isozyme hCA IX (h = human). Against hCA I these compounds were either micromolar or low-nanomolar inhibitors, while against hCA II and IX inhibition in the range of 6.8-53 and 9.7-107 nM, respectively, was observed. The most potent inhibitor against hCA IX was the galactose derivative 8 (K-i = 9.7 nM); this is so far the most potent glycoconjugate inhibitor reported for the tumor-associated hCA IX. These carbohydrate-tethered sulfonamides may prove interesting lead candidates to target tumor-associated CA isozymes, wherein the CA domain is located extracellularly.
• Synthesis and<i>in vitro</i>Evaluation of Novel Galactosyl-triazolo-benzenesulfonamides Against<i>Trypanosoma cruzi</i>
  作者：Getúlio G. Junqueira、Marcelo R. Carvalho、Peterson de Andrade、Carla D. Lopes、Zumira A. Carneiro、Renata Sesti-Costa、João S. Silva、Ivone Carvalho

  DOI：10.5935/0103-5053.20140158

  日期：——

  The only drugs approved for the treatment of Chagas disease, nifurtimox and benznidazole, present toxic side effects and limited efficacy in the chronic stage of the disease, which highlight the need for new drugs. Amongst the different molecular drug targets discovered in the parasite, Trypanosoma cruzi trans-sialidase (TcTS) has been considered crucial in the recognition and invasion of host cells. Hence, we report the efficient synthesis and biological evaluation (TcTS inhibition and antitrypanosomal activities) of some galactose-containing triazol-arylsulfonamides via microwave-assisted Cu(I) 1,3-dipolar azide-alkyne cycloaddition (CuAAC) based on azide benzenesulfonamides and a galactose-derived alkyne as precursors. Most of the compounds tested against TcTS showed moderate to weak inhibition (40%-15%), except one of the compounds (81%). Regarding the antitrypanosomal assay, some compounds [(IC50 70.9 mu M) and (IC50 44.0 mu M)] exhibited the most significant activities, although not as active as benznidazole (IC50 1.4 mu M). Nevertheless, the cytotoxicity assessment showed that all compounds were not cytotoxic. In this preliminary work, we considered some compounds as lead scaffolds for further optimization.