2-(2-nitro-imidazol-1-yl)-N-(4-sulfamoylphenyl)acetamide | 1383370-94-2

• 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: 2-(2-nitro-imidazol-1-yl)-N-(4-sulfamoylphenyl)acetamide
• 英文别名: US8980932, 4a (DH296)；2-(2-nitroimidazol-1-yl)-N-(4-sulfamoylphenyl)acetamide
• CAS: 1383370-94-2
• 化学式: C₁₁H₁₁N₅O₅S
• 分子量: 325.305
• InChiKey: HUFRGRVXHRXCPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  161
• 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)acetate 在 4-二甲氨基吡啶 、 茴香硫醚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 48.0h， 生成 2-(2-nitro-imidazol-1-yl)-N-(4-sulfamoylphenyl)acetamide
  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

• CANCER TARGETING USING CARBONIC ANHYDRASE ISOFORM IX INHIBITORS
  申请人：Lambin Philippe

  公开号：US20130274305A1

  公开（公告）日：2013-10-17

  The present invention concerns novel carbonic anhydrase IX inhibitors comprising a nitroimidazole moiety and their use in therapy of hypoxic conditions, in particular cancer treatment, especially chemotherapy and radiotherapy. The compounds of the invention have an increased specificity for the carbonic anhydrase IX enzyme compared to the art. The present invention relates to novel nitroimidazole derivates represented by formula (1).

  本发明涉及一种新型碳酸酐酶IX抑制剂，其中包括亚硝基咪唑基团，并且其在治疗低氧条件，特别是癌症治疗，尤其是化疗和放疗方面的应用。该发明的化合物与现有技术相比具有更高的碳酸酐酶IX酶的特异性。本发明涉及由式（1）表示的新型亚硝基咪唑衍生物。
• [EN] CANCER TARGETING USING CARBONIC ANHYDRASE ISOFORM IX INHIBITORS<br/>[FR] CIBLAGE DE CANCER UTILISANT DES INHIBITEURS D'ISOFORME IX D'ANHYDRASE CARBONIQUE
  申请人：STICHTING MAASTRICHT RADIATION ONCOLOGY MAASTRO CLINIC

  公开号：WO2012087115A8

  公开（公告）日：2013-09-19
• US8980932B2
  申请人：——

  公开号：US8980932B2

  公开（公告）日：2015-03-17
• 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.