N-[2-(2-nitro-imidazol-1-yl)ethyl]sulfamide | 1476737-84-4

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: N-[2-(2-nitro-imidazol-1-yl)ethyl]sulfamide
• 英文别名: 2-Nitro-1-[2-(sulfamoylamino)ethyl]imidazole；2-nitro-1-[2-(sulfamoylamino)ethyl]imidazole
• CAS: 1476737-84-4
• 化学式: C₅H₉N₅O₄S
• 分子量: 235.224
• InChiKey: QBYDXIGCRLBJTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tert-butyl (2-(2-nitro-1H-imidazol-1-yl)ethyl)carbamate 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 反应 2.0h， 生成 N-[2-(2-nitro-imidazol-1-yl)ethyl]sulfamide
  参考文献：
  名称：

  Hypoxia-Targeting Carbonic Anhydrase IX Inhibitors by a New Series of Nitroimidazole-Sulfonamides/Sulfamides/Sulfamates

  摘要：

  A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on the complex of hCA II with the lead sulfamide derivative of this series clarified the binding mode of this type of inhibitors in the enzyme active site cavity. Some of the best nitroimidazole CA IX inhibitors showed significant activity in vitro by reducing hypoxia-induced extracellular acidosis in HT-29 and HeLa cell lines. In vivo testing of the lead molecule in the sulfamide series, in cotreatment with doxorubicin, demonstrated a chemosensitization of CA IX containing tumors. Such CA inhibitors, specifically targeting the tumor-associated isoforms, are candidates for novel treatment strategies against hypoxic tumors overexpressing extracellular CA isozymes.

  DOI：

  10.1021/jm4009532

文献信息

• Hypoxia-Targeting Carbonic Anhydrase IX Inhibitors by a New Series of Nitroimidazole-Sulfonamides/Sulfamides/Sulfamates
  作者：Marouan Rami、Ludwig Dubois、Nanda-Kumar Parvathaneni、Vincenzo Alterio、Simon J. A. van Kuijk、Simona Maria Monti、Philippe Lambin、Giuseppina De Simone、Claudiu T. Supuran、Jean-Yves Winum

  DOI：10.1021/jm4009532

  日期：2013.11.14

  A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on the complex of hCA II with the lead sulfamide derivative of this series clarified the binding mode of this type of inhibitors in the enzyme active site cavity. Some of the best nitroimidazole CA IX inhibitors showed significant activity in vitro by reducing hypoxia-induced extracellular acidosis in HT-29 and HeLa cell lines. In vivo testing of the lead molecule in the sulfamide series, in cotreatment with doxorubicin, demonstrated a chemosensitization of CA IX containing tumors. Such CA inhibitors, specifically targeting the tumor-associated isoforms, are candidates for novel treatment strategies against hypoxic tumors overexpressing extracellular CA isozymes.