[1-(4-sulfamoyl-phenyl)-1H-[1,2,3]-triazol-4-ylmethyl]carbamic acid tert-butyl ester | 1613266-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [1-(4-sulfamoyl-phenyl)-1H-[1,2,3]-triazol-4-ylmethyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[[1-(4-sulfamoylphenyl)triazol-4-yl]methyl]carbamate
• CAS: 1613266-94-6
• 化学式: C₁₄H₁₉N₅O₄S
• 分子量: 353.402
• InChiKey: WVZZXHWZHTXPEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [1-(4-sulfamoyl-phenyl)-1H-[1,2,3]-triazol-4-ylmethyl]carbamic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以100%的产率得到4-(4-(aminomethyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide hydrochloride
  参考文献：
  名称：

  Carbonic Anhydrase Inhibition with Benzenesulfonamides and Tetrafluorobenzenesulfonamides Obtained via Click Chemistry

  摘要：

  A series of novel benzene- and 2,3,5,6-tetrafluorobenzenesulfonamide was synthesized by using a click chemistry approach starting from azido-substituted sulfonamides and alkynes, incorporating aryl, alkyl, cycloalkyl, and amino-/hydroxy-/halogenoalkyl moieties. The new compounds were medium potency inhibitors of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and low nanomolar/subnanomolar inhibitors of the tumor-associated hCA IX and XII isoforms. The X-ray crystal structure of two such sulfonamides in adduct with hCA II allowed us to understand the factors governing inhibitory power.

  DOI：

  10.1021/ml500196t
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 铜 、 四甲基氯化铵 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 5.0h， 生成 [1-(4-sulfamoyl-phenyl)-1H-[1,2,3]-triazol-4-ylmethyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Fluorescent sulfonamide carbonic anhydrase inhibitors incorporating 1,2,3-triazole moieties: Kinetic and X-ray crystallographic studies

  摘要：

  Fluorescent sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) were essential for demonstrating the role played by the tumor-associated isoform CA IX in acidification of tumors, cancer progression towards metastasis and for the development of imaging and therapeutic strategies for the management of hypoxic tumors which overexpress CA IX. However, the presently available such compounds are poorly water soluble which limits their use. Here we report new fluorescent sulfonamides 7, 8 and 10 with increased water solubility. The new derivatives showed poor hCA I inhibitory properties, but were effective inhibitors against the hCA II (K(I)s of 366-127 nM), CA IX (K(I)s of 8.1-36.9 nM), CA XII (K(I)s of 4.1-20.5 nM) and CA XIV (K(I)s of 12.8-53.6 nM). A high resolution X-ray crystal structure of one of these compounds bound to hCA II revealed the factors associated with the good inhibitory properties. Furthermore, this compound showed a three-fold increase of water solubility compared to a similar derivative devoid of the triazole moiety, making it an interesting candidate for ex vivo/in vivo studies. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.031

文献信息

• Design and synthesis of sulfonamides incorporating a biotin moiety: Carbonic anhydrase inhibitory effects, antiproliferative activity and molecular modeling studies
  作者：Paloma Begines、Alessandro Bonardi、Alessio Nocentini、Paola Gratteri、Simone Giovannuzzi、Roberto Ronca、Camilla Tavani、Maria Luisa Massardi、Óscar López、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2023.117467

  日期：2023.10

  Sulfonamides constitute an important class of classical carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. Herein we have accomplished the conjugation of biotin with an ample number of sulfonamide motifs with the aim of testing them in vitro as inhibitors of the human carbonic anhydrase (hCA) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Most

  磺胺类药物是一类重要的经典碳酸酐酶 (CA、EC 4.2.1.1) 抑制剂。在此，我们完成了生物素与大量磺酰胺基序的缀合，目的是在体外测试它们作为人碳酸酐酶 (hCA) 同工型 I 和 II（胞质同工酶）以及 hCA IX 和 XII 的抑制剂。跨膜、肿瘤相关酶）。大多数这些新合成的化合物表现出令人感兴趣的抑制特性，其活性在纳摩尔范围内。SLC-0111 中也发现了 4-FC 6 H 4部分的存在，对肿瘤相关缺氧诱导的 hCA 同工型 XII 具有出色的选择性，抑制常数 (K I ) 为 4.5 nM。2-萘基衍生物是最有效的 hCA IX 抑制剂 (K I = 6.2 nM)，比 AAZ (K I = 25 nM) 强 4 倍， 且选择性非常好。选择一些化合物对一组 3 种人类肿瘤细胞系进行抗增殖活性测试，其中一种化合物对胶质母细胞瘤、三阴性乳腺癌和胰腺癌细胞系显示出抗增殖活性。
• Carbonic Anhydrase Inhibition with Benzenesulfonamides and Tetrafluorobenzenesulfonamides Obtained via Click Chemistry
  作者：Nicolino Pala、Laura Micheletto、Mario Sechi、Mayank Aggarwal、Fabrizio Carta、Robert McKenna、Claudiu T. Supuran

  DOI：10.1021/ml500196t

  日期：2014.8.14

  A series of novel benzene- and 2,3,5,6-tetrafluorobenzenesulfonamide was synthesized by using a click chemistry approach starting from azido-substituted sulfonamides and alkynes, incorporating aryl, alkyl, cycloalkyl, and amino-/hydroxy-/halogenoalkyl moieties. The new compounds were medium potency inhibitors of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and low nanomolar/subnanomolar inhibitors of the tumor-associated hCA IX and XII isoforms. The X-ray crystal structure of two such sulfonamides in adduct with hCA II allowed us to understand the factors governing inhibitory power.
• Fluorescent sulfonamide carbonic anhydrase inhibitors incorporating 1,2,3-triazole moieties: Kinetic and X-ray crystallographic studies
  作者：Fabrizio Carta、Marta Ferraroni、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2015.11.031

  日期：2016.1

  Fluorescent sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors (CAIs) were essential for demonstrating the role played by the tumor-associated isoform CA IX in acidification of tumors, cancer progression towards metastasis and for the development of imaging and therapeutic strategies for the management of hypoxic tumors which overexpress CA IX. However, the presently available such compounds are poorly water soluble which limits their use. Here we report new fluorescent sulfonamides 7, 8 and 10 with increased water solubility. The new derivatives showed poor hCA I inhibitory properties, but were effective inhibitors against the hCA II (K(I)s of 366-127 nM), CA IX (K(I)s of 8.1-36.9 nM), CA XII (K(I)s of 4.1-20.5 nM) and CA XIV (K(I)s of 12.8-53.6 nM). A high resolution X-ray crystal structure of one of these compounds bound to hCA II revealed the factors associated with the good inhibitory properties. Furthermore, this compound showed a three-fold increase of water solubility compared to a similar derivative devoid of the triazole moiety, making it an interesting candidate for ex vivo/in vivo studies. (C) 2015 Elsevier Ltd. All rights reserved.