4-(diprop-2-yn-1-ylamino)benzenesulfonamide

• 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: 4-(diprop-2-yn-1-ylamino)benzenesulfonamide
• 英文别名: 4-(diprop-2-ynylamino)benzenesulfonamide；4-[Bis(prop-2-ynyl)amino]benzenesulfonamide；4-[bis(prop-2-ynyl)amino]benzenesulfonamide
• 化学式: C₁₂H₁₂N₂O₂S
• 分子量: 248.305
• InChiKey: BBQOSXJFQHQFIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(diprop-2-yn-1-ylamino)benzenesulfonamide 、 齐多夫定 在 铜 、 四甲基氯化铵 作用下， 以 水 、 叔丁醇 为溶剂， 以32%的产率得到4-(bis((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)amino)benzenesulfonamide
  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：

  N'-((4-aminophenyl)sulfonyl)-N,N-dimethylformimidamide 在 potassium carbonate 、 异丙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 4-(diprop-2-yn-1-ylamino)benzenesulfonamide
  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

文献信息

• A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects
  作者：Fabrizio Carta、Lorenzo Di Cesare Mannelli、Melissa Pinard、Carla Ghelardini、Andrea Scozzafava、Robert McKenna、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2015.02.027

  日期：2015.4

  with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) of which multiple isoforms are known, and some appear to be involved in pain. These sulfonamides showed modest inhibition against the cytosolic isoform CA I, but were generally effective, low nanomolar CA II, VII, IX and XII

  据报道，一系列苯磺酰胺碳酸酐酶（CA，EC 4.2.1.1）抑制剂结合了亲脂性的4-烷氧基和4-芳氧基部分，以及乙氧唑酰胺和磺胺的几种衍生物。研究了这些衍生物作为金属酶碳酸酐酶（CA，EC 4.2.1.1）的抑制剂，已知这些化合物有多种同工型，有些似乎与疼痛有关。这些磺酰胺类药物对胞质同工型CA I表现出适度的抑制作用，但通常是有效的低纳摩尔CA II，VII，IX和XII抑制剂。几种此类磺酰胺与CA II加成物的X射线晶体学数据使我们能够合理化良好的抑制数据。在由奥沙利铂引起的神经性疼痛的小鼠模型中，此处报道的一种强力的CA II / VII抑制剂诱导了持久的止痛作用，这一事实以前从未观察到。这是合理设计的具有镇痛有效调节作用的磺酰胺CA抑制剂的首次报道。
• 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.