N-(4-methoxybenzenesulfonyl)-N-{[2-(4-sulfamoylphenyl)ethylcarbamoyl]methyl}-aminoacetohydroxamic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-methoxybenzenesulfonyl)-N-{[2-(4-sulfamoylphenyl)ethylcarbamoyl]methyl}-aminoacetohydroxamic acid
• 英文别名: 2-[hydroxycarbamoylmethyl-(4-methoxy-benzenesulfonyl)-amino]-N-[2-(4-sulfamoyl-phenyl)-ethyl]-acetamide；2-[[2-(hydroxyamino)-2-oxoethyl]-(4-methoxyphenyl)sulfonylamino]-N-[2-(4-sulfamoylphenyl)ethyl]acetamide
• 化学式: C₁₉H₂₄N₄O₈S₂
• 分子量: 500.554
• InChiKey: QSOYTCHABFMDFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  202
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-(2-氨乙基)苯磺酰胺 在 N-甲基吗啉 、 氯甲酸乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 N-(4-methoxybenzenesulfonyl)-N-{[2-(4-sulfamoylphenyl)ethylcarbamoyl]methyl}-aminoacetohydroxamic acid
  参考文献：
  名称：

  碳酸酐酶抑制剂：亚氨基二乙酸羧酸盐/异羟肟酸酯也结合了苯磺酰胺部分，可抑制胞质/肿瘤相关的同工型I，II和IX。

  摘要：

  据报道，新型磺酰胺碳酸酐酶（CA，EC 4.2.1.1）抑制剂（CAI）的合成，其分子中还具有羧酸盐/异羟肟酸酯部分。这些化合物可能作用于双重抗肿瘤靶标，肿瘤相关的CA同工酶（CA IX）和某些基质金属蛋白酶（MMP）。这些化合物是从亚氨基二乙酸开始采用原始方法制备的，并作为三种同功酶hCA I，II（胞质）和IX（跨膜）的抑制剂进行了分析。新衍生物显示出对同工酶I（K（I）s在95-8300 nM范围内）的弱抑制活性，对中型CA II抑制剂（K（I）s在8.4-65 nM范围内）极好，并且非常好的选择性CA IX抑制剂（K（I）范围为3.8-26 nM）。

  DOI：

  10.1016/j.bmcl.2006.12.107

文献信息

• Dual Inhibitors of Matrix Metalloproteinases and Carbonic Anhydrases: Iminodiacetyl-Based Hydroxamate−Benzenesulfonamide Conjugates
  作者：Sérgio M. Marques、Elisa Nuti、Armando Rossello、Claudiu T. Supuran、Tiziano Tuccinardi、Adriano Martinelli、M. Amélia Santos

  DOI：10.1021/jm800964f

  日期：2008.12.25

  Matrix metalloproteinases (MMPs) and carbonic anhydrases (CAs) are two classes of zinc enzymes with different roles and catalytic targets, such as the degradation of most of the extracellular matrix (ECM) proteins and the regulation of the CO2/HCO3- equilibrium in the cells, respectively. Both families have isoforms which were proved to be involved in several stages of carcinogenic processes, and so the selective inhibition of these enzymes might be of interest in cancer therapy. We report herein the design, synthesis, and in vitro evaluation of a series Of Compounds possessing the iminodiacetic acid as the main backbone and two functional groups attached, namely, the hydroxamic acid and the arylsulfonamide (ArSO2NH2) moieties, to enable the inhibition of MMPs and CAs, respectively. These compounds were demonstrated to strongly inhibit both MMPs and CAs, some of them from the nanomolar to subnanomolar range. Furthermore, a docking study for MMPs was reported for the most promising compound in order to investigate its binding interactions with the different MMPs.