prop-2-ynyl 4-sulfamoylbenzoate | 915694-58-5

• 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: prop-2-ynyl 4-sulfamoylbenzoate
• CAS: 915694-58-5
• 化学式: C₁₀H₉NO₄S
• mdl: MFCD27932599
• 分子量: 239.252
• InChiKey: IORJVPBKDUGFOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  prop-2-ynyl 4-sulfamoylbenzoate 、 齐多夫定 在 铜 、 四甲基氯化铵 作用下， 以 水 、 叔丁醇 为溶剂， 以30%的产率得到(1-(2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl 4-sulfamoylbenzoate
  参考文献：
  名称：

  Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors

  摘要：

  Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7h, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with K-I values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC(50 )values ranging from 5.2 to 9.1 mu M). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.

  DOI：

  10.1021/acs.jmedchem.0c00636
• 作为产物：
  描述：

  对羧基苯磺酰胺 、 2-丙炔-1-醇 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以38%的产率得到prop-2-ynyl 4-sulfamoylbenzoate
  参考文献：
  名称：

  A Novel Class of Carbonic Anhydrase Inhibitors:  Glycoconjugate Benzene Sulfonamides Prepared by “Click-Tailing”

  摘要：

  Aryl and heteroaryl sulfonamides (ArSO2NH2) are therapeutically used to inhibit the catalytic activity of carbonic anhydrases (CAs). Using a "click- tail" approach a novel class of glycoconjugate benzene sulfonamides have been synthesized that contain diverse carbohydrate- triazole tails. These compounds were assessed for their ability to inhibit three human CA isozymes in vitro: cytosolic hCA I and hCA II and transmembrane, tumor- associated hCA IX. This isozyme has a minimal expression in normal tissue but is overexpressed in hypoxic tumors and its inhibition is a current approach toward new cancer therapies. The qualitative structure- activity for all derivatives demonstrated that the stereochemical diversity present within the carbohydrate tails effectively interrogated the CA active site topology, to generate several inhibitors that were potent and selective toward hCA IX, an important outcome in the quest for potential cancer therapy applications based on CA inhibition.

  DOI：

  10.1021/jm060967z

文献信息

• Anti-mycobacterial activity of a bis-sulfonamide
  作者：Brendan L. Wilkinson、Laurent F. Bornaghi、Anthony D. Wright、Todd A. Houston、Sally-Ann Poulsen

  DOI：10.1016/j.bmcl.2006.11.079

  日期：2007.3

  A bis-arylsulfonamide, 7, has been identified that exhibits growth inhibition of Mycobacterium smegmatis at less than 25 microg/mL, but has no such activity against Escherichia coli or Staphylococcus aureus. A closely related bis-arylsulfonamide (8) was much less active, but was the only other compound among 54 arylsulfonamides tested with detectable growth inhibition of M. smegmatis.
• A Novel Class of Carbonic Anhydrase Inhibitors:  Glycoconjugate Benzene Sulfonamides Prepared by “Click-Tailing”
  作者：Brendan L. Wilkinson、Laurent F. Bornaghi、Todd A. Houston、Alessio Innocenti、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1021/jm060967z

  日期：2006.11.1

  Aryl and heteroaryl sulfonamides (ArSO2NH2) are therapeutically used to inhibit the catalytic activity of carbonic anhydrases (CAs). Using a "click- tail" approach a novel class of glycoconjugate benzene sulfonamides have been synthesized that contain diverse carbohydrate- triazole tails. These compounds were assessed for their ability to inhibit three human CA isozymes in vitro: cytosolic hCA I and hCA II and transmembrane, tumor- associated hCA IX. This isozyme has a minimal expression in normal tissue but is overexpressed in hypoxic tumors and its inhibition is a current approach toward new cancer therapies. The qualitative structure- activity for all derivatives demonstrated that the stereochemical diversity present within the carbohydrate tails effectively interrogated the CA active site topology, to generate several inhibitors that were potent and selective toward hCA IX, an important outcome in the quest for potential cancer therapy applications based on CA inhibition.
• Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors
  作者：Emanuela Berrino、Andrea Angeli、Dmitry D. Zhdanov、Anna P. Kiryukhina、Andrea Milaneschi、Alessandro De Luca、Murat Bozdag、Simone Carradori、Silvia Selleri、Gianluca Bartolucci、Thomas S. Peat、Marta Ferraroni、Claudiu T. Supuran、Fabrizio Carta

  DOI：10.1021/acs.jmedchem.0c00636

  日期：2020.7.9

  Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7h, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with K-I values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC(50 )values ranging from 5.2 to 9.1 mu M). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.