4-[4-(aminosulfonyl)phenyl]-1-(β-D-galactopyranosyl)-1H-1,2,3-triazole | 1017276-62-8

• 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-(β-D-galactopyranosyl)-1H-1,2,3-triazole
• 英文别名: 4-[1-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]triazol-4-yl]benzenesulfonamide
• CAS: 1017276-62-8
• 化学式: C₁₄H₁₈N₄O₇S
• 分子量: 386.386
• InChiKey: OHQURRXQRSULTO-MBJXGIAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  189
• 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',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-1H-1,2,3-triazole 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以98%的产率得到4-[4-(aminosulfonyl)phenyl]-1-(β-D-galactopyranosyl)-1H-1,2,3-triazole
  参考文献：
  名称：

  A Prodrug Approach Toward Cancer-Related Carbonic Anhydrase Inhibition

  摘要：

  The selective inhibition of cancer-associated human carbonic anhydrase (CA) enzymes, specifically CA IX and XII, has been validated as a mechanistically novel approach toward personalized cancer management. Herein we report the design and synthesis of a panel of 24 novel glycoconjugate primary sulfonamides that bind to the extracellular catalytic domain of CA IX and XII. These compounds were synthesized from variably acylated glycopyranosyl azides and either 3- or 4-ethynyl benzene sulfonamide using Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC). The CA enzyme inhibition profile for all compounds was determined, while in vitro metabolic stability, plasma stability, and plasma protein binding for a representative set of compounds was measured. Our findings demonstrate the influence of the differing acyl groups on these key biopharmaceutical properties, confirming that acyl group protected carbohydrate-based sulfonamides have potential as prodrugs for selectively targeting the extracellular cancer-associated CA enzymes.

  DOI：

  10.1021/jm401163e

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.
• A Prodrug Approach Toward Cancer-Related Carbonic Anhydrase Inhibition
  作者：Cindy J. Carroux、Gregory M. Rankin、Janina Moeker、Laurent F. Bornaghi、Kasiram Katneni、Julia Morizzi、Susan A. Charman、Daniela Vullo、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1021/jm401163e

  日期：2013.12.12

  The selective inhibition of cancer-associated human carbonic anhydrase (CA) enzymes, specifically CA IX and XII, has been validated as a mechanistically novel approach toward personalized cancer management. Herein we report the design and synthesis of a panel of 24 novel glycoconjugate primary sulfonamides that bind to the extracellular catalytic domain of CA IX and XII. These compounds were synthesized from variably acylated glycopyranosyl azides and either 3- or 4-ethynyl benzene sulfonamide using Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC). The CA enzyme inhibition profile for all compounds was determined, while in vitro metabolic stability, plasma stability, and plasma protein binding for a representative set of compounds was measured. Our findings demonstrate the influence of the differing acyl groups on these key biopharmaceutical properties, confirming that acyl group protected carbohydrate-based sulfonamides have potential as prodrugs for selectively targeting the extracellular cancer-associated CA enzymes.