4-(4-{[β-D-glucopyranosyl]sulfonylmethyl}-1-H-1,2,3-triazol-1-yl)benzenesulfonamide | 1159102-06-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-{[β-D-glucopyranosyl]sulfonylmethyl}-1-H-1,2,3-triazol-1-yl)benzenesulfonamide
• 英文别名: p-(4-{[β-D-glucopyranosyl]sulfonylmethyl}-1H-1,2,3-triazol-1-yl)benzenesulfonamide；4-(4-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-ylsulfonyl)methyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide；4-[4-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]sulfonylmethyl]triazol-1-yl]benzenesulfonamide
• CAS: 1159102-06-3
• 化学式: C₁₅H₂₀N₄O₉S₂
• 分子量: 464.477
• InChiKey: RZPFPVJFFHHVJK-QMIVOQANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  232
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  4-(4-{[2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl]sulfonylmethyl}-1-H-1,2,3-triazol-1-yl)benzenesulfonamide 在 甲醇 、 sodium methylate 作用下， 以93%的产率得到4-(4-{[β-D-glucopyranosyl]sulfonylmethyl}-1-H-1,2,3-triazol-1-yl)benzenesulfonamide
  参考文献：
  名称：

  Targeting Hypoxic Tumor Cell Viability with Carbohydrate-Based Carbonic Anhydrase IX and XII Inhibitors

  摘要：

  Carbonic anhydrase (CA) enzymes, specifically membrane-bound isozymes CA IX and CA XII, underpin a pH-regulating system that enables hypoxic tumor cell survival and proliferation. CA IX and XII are implicated as potential targets for the development of new hypoxic cancer therapies. To date, only a few small molecules have been characterized in CA-relevant cell and animal model systems. In this paper, we describe the development of a new class of carbohydrate-based small molecule CA inhibitors, many of which inhibit CA IX and XII within a narrow range of low nanomolar K-i values (5.3-11.2 nM). We evaluate for the first time carbohydrate-based CA inhibitors in cell-based models that emulate the protective role of CA IX in an acidic tumor microenvironment. Our findings identified two inhibitors (compounds 5 and 17) that block CA IX-induced survival and have potential for development as in vivo cancer cell selective inhibitors.

  DOI：

  10.1021/jm200892s

文献信息

• Inhibition of carbonic anhydrase isozymes with benzene sulfonamides incorporating thio, sulfinyl and sulfonyl glycoside moieties
  作者：Mathilde Singer、Marie Lopez、Laurent F. Bornaghi、Alessio Innocenti、Daniela Vullo、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1016/j.bmcl.2009.02.086

  日期：2009.4

  A series of benzene sulfonamides incorporating thio, sulfinyl or sulfonyl glycoside moieties were synthesized. These glycoconjugates were investigated for their ability to inhibit the enzymatic activity of four human carbonic anhydrases (hCA): isozymes I, II and tumour-associated isozymes IX and XII. The oxidation state of the sulfur in the carbohydrate tail moiety did not influence either enzyme inhibition potency or isozyme selectivity even though presenting opportunities for differing interactions with the target isozymes. (c) 2009 Elsevier Ltd. All rights reserved.
• Targeting Hypoxic Tumor Cell Viability with Carbohydrate-Based Carbonic Anhydrase IX and XII Inhibitors
  作者：Jason C. Morris、Johanna Chiche、Caroline Grellier、Marie Lopez、Laurent F. Bornaghi、Alfonso Maresca、Claudiu T. Supuran、Jacques Pouysségur、Sally-Ann Poulsen

  DOI：10.1021/jm200892s

  日期：2011.10.13

  Carbonic anhydrase (CA) enzymes, specifically membrane-bound isozymes CA IX and CA XII, underpin a pH-regulating system that enables hypoxic tumor cell survival and proliferation. CA IX and XII are implicated as potential targets for the development of new hypoxic cancer therapies. To date, only a few small molecules have been characterized in CA-relevant cell and animal model systems. In this paper, we describe the development of a new class of carbohydrate-based small molecule CA inhibitors, many of which inhibit CA IX and XII within a narrow range of low nanomolar K-i values (5.3-11.2 nM). We evaluate for the first time carbohydrate-based CA inhibitors in cell-based models that emulate the protective role of CA IX in an acidic tumor microenvironment. Our findings identified two inhibitors (compounds 5 and 17) that block CA IX-induced survival and have potential for development as in vivo cancer cell selective inhibitors.