4-[2-(苯亚甲基氨基)乙基]苯磺酰胺 | 834917-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[2-(苯亚甲基氨基)乙基]苯磺酰胺
• 英文名称: 4-[2-(benzylidene-imino)-ethyl]-benzenesulfonamide
• 英文别名: 4-(2-((benzylidene)amino)ethyl)benzenesulfonamide；4-{2-[(E)-Benzylideneamino]ethyl}benzene-1-sulfonamide；4-[2-(benzylideneamino)ethyl]benzenesulfonamide
• CAS: 834917-19-0
• 化学式: C₁₅H₁₆N₂O₂S
• 分子量: 288.37
• InChiKey: PLCQVPWOCPLUCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  80.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[2-(苯亚甲基氨基)乙基]苯磺酰胺 在 sodium tetrahydroborate 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 丙酮 、 乙腈 为溶剂， 反应 17.5h， 生成 N-benzyl-2-(dibenzylamino)-N-(4-sulfamoylphenethyl)-acetamide
  参考文献：
  名称：

  通过三尾法设计的人碳酸酐酶的磺酰胺抑制剂：改善配体/同工型匹配和作用选择性。

  摘要：

  “尾巴方法”已成为人类碳酸酐酶抑制剂（hCAI）设计用于各种治疗药物（包括抗青光眼药物）的里程碑。除了hCAs活性位点的经典疏水/亲水区分开，在中间/外部活性位点边缘还发现了一些亚口袋，可以用于增加CAI同工型的选择性。三尾苯磺酰胺CAI（TTI）在这里探讨了这种假设，以充分利用hCA之间的这种氨基酸差异。在此概念验证研究中，我们对32种在尾部组合方面不同的苯磺酰胺进行了广泛的构效关系（SAR）研究，并分析了它们对hCAs I，II，IV和XII的抑制作用。通过X射线晶体学和计算机模拟进行了结构研究评估配体/靶标相互作用模式的工具。在该疾病的兔子模型中评估了与青光眼有关的同工型的最有效和选择性抑制剂，该抑制剂可实现与临床使用的多佐胺相当的眼内压降低作用。

  DOI：

  10.1021/acs.jmedchem.0c00733
• 作为产物：
  描述：

  苯甲醛 、 4-(2-氨乙基)苯磺酰胺 以 甲醇 为溶剂， 反应 4.0h， 生成 4-[2-(苯亚甲基氨基)乙基]苯磺酰胺
  参考文献：
  名称：

  通过三尾法设计的人碳酸酐酶的磺酰胺抑制剂：改善配体/同工型匹配和作用选择性。

  摘要：

  “尾巴方法”已成为人类碳酸酐酶抑制剂（hCAI）设计用于各种治疗药物（包括抗青光眼药物）的里程碑。除了hCAs活性位点的经典疏水/亲水区分开，在中间/外部活性位点边缘还发现了一些亚口袋，可以用于增加CAI同工型的选择性。三尾苯磺酰胺CAI（TTI）在这里探讨了这种假设，以充分利用hCA之间的这种氨基酸差异。在此概念验证研究中，我们对32种在尾部组合方面不同的苯磺酰胺进行了广泛的构效关系（SAR）研究，并分析了它们对hCAs I，II，IV和XII的抑制作用。通过X射线晶体学和计算机模拟进行了结构研究评估配体/靶标相互作用模式的工具。在该疾病的兔子模型中评估了与青光眼有关的同工型的最有效和选择性抑制剂，该抑制剂可实现与临床使用的多佐胺相当的眼内压降低作用。

  DOI：

  10.1021/acs.jmedchem.0c00733

文献信息

• Carbonic anhydrase inhibitors. Inhibition of human cytosolic isoforms I and II with (reduced) Schiff’s bases incorporating sulfonamide, carboxylate and carboxymethyl moieties
  作者：Gihane Nasr、Alina Cristian、Mihail Barboiu、Daniella Vullo、Jean-Yves Winum、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2014.03.041

  日期：2014.5

  cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes, hCA I and II. The Ki values of the Schiff bases were in the range of 7.0–21,400 nM against hCA II and of 52–8600 nM against hCA I, respectively. The corresponding amines showed Ki values in the range of 8.6 nM–5.3 μM against hCA II, and of 18.7–251 nM against hCA I, respectively. Unlike the imines, the reduced Schiff bases are stable to hydrolysis

  通过将掺入磺酰胺，羧酸或羧甲基官能团作为Zn 2+结合基团的芳族胺与掺入叔丁基，羟基和/或甲氧基的芳族醛缩合来合成席夫碱的文库。然后通过亚胺的还原获得相应的胺。测定了这些化合物对两种胞质人碳酸酐酶（hCA，EC 4.2.1.1）同工酶hCA I和II的抑制作用。相对于hCA II，席夫碱的K i值分别在7.0–21,400 nM和针对hCA I的52–8600 nM的范围内。相应的胺显示K i抗hCA II的值分别为8.6 nM–5.3μM，抗hCA I的值分别为18.7–251 nM。与亚胺不同，还原的席夫碱对水解稳定，并且检测到了几种低纳摩尔抑制剂，其中大多数掺入了磺酰胺基。一些羧酸盐还显示出有趣的CA抑制特性。这样的水溶性衍生物可以显示出药理学应用。
• Development of Hydrogen Sulfide-Releasing Carbonic Anhydrases IX- and XII-Selective Inhibitors with Enhanced Antihyperalgesic Action in a Rat Model of Arthritis
  作者：Alessandro Bonardi、Laura Micheli、Lorenzo Di Cesare Mannelli、Carla Ghelardini、Paola Gratteri、Alessio Nocentini、Claudiu T. Supuran

  DOI：10.1021/acs.jmedchem.2c00982

  日期：2022.10.13

  CAs I, II, IV, IX, and XII, showing a markedly increased inhibition potency/isoform selectivity compared to the CAI synthetic precursors. The best compounds demonstrated the ability to consistently release H2S and produce a potent pain-relieving effect in a rat model of arthritis. Compound 26 completely reverted the pain state 45 min after administration with enhanced antihyperalgesic effect in vivo compared

  本文提出了一种基于硫化氢 (H 2 S)的抗炎作用和抑制碳酸酐酶 (CAs) IX 和 XII 的有效治疗方法来治疗关节炎。H 2 S 是一种人体气体递质，可在低浓度下调节炎症反应。抑制 CA IX 和 XII 可以恢复酸性发炎滑液中的正常 pH 值，从而减轻关节炎症状。我们在此报告了 H 2 S 供体─CA 抑制剂 (CAI) 杂化衍生物的设计。后者在体外作为人类 CA I、II、IV、IX 和 XII 的抑制剂进行了测试，与 CAI 合成前体相比，显示出显着增加的抑制效力/异构体选择性。最好的化合物表现出持续释放 H 的能力2 S 并在关节炎大鼠模型中产生有效的疼痛缓解作用。与单一H 2 S供体、CAI片段或其共同给药相比，化合物26在给药后45分钟完全恢复疼痛状态，具有增强的体内抗痛觉过敏作用。
• Benzenesulfonamide derivatives as potent acetylcholinesterase, α-glycosidase, and glutathione S-transferase inhibitors: biological evaluation and molecular docking studies
  作者：Parham Taslimi、Mesut Işık、Fikret Türkan、Mustafa Durgun、Cüneyt Türkeş、İlhami Gülçin、Şükrü Beydemir

  DOI：10.1080/07391102.2020.1790422

  日期：2021.10.13

  Sulfonamide derivatives exhibit a wide biological activity and can function as potential medical molecules in the development of a drug. Studies have reported that the compounds have an effect on many enzymes. In this study, the derivatives of amine sulfonamide (1i-11i) were prepared with reduced imine compounds (1-11) with NaBH4 in methanol. The synthesized compounds were fully characterized by spectral data and analytical. The effect of the synthesized derivatives on acetylcholinesterase (AChE), glutathione S-transferase (GST) and a-glycosidase (alpha-GLY) enzymes were determined. For the AChE and alpha-GLY, the most powerful inhibition was observed on 10 and 10i series with K-I value in the range 2.26 +/- 0.45-3.57 +/- 0.97 and 95.73 +/- 13.67-102.45 +/- 11.72 mu M, respectively. K-I values of the series for GST were found in the range of 22.76 +/- 1.23-49.29 +/- 4.49. Finally, the compounds have a stronger inhibitor in lower concentrations by the attachment of functional electronegative groups such as two halogens (-Br and -CI), -OH to the benzene ring and -SO2NH2. The crystal structures of AChE, alpha-GLY, and GST in complex with selected derivatives 4 and 10 show the importance of the functional moieties in the binding modes within the receptors.
• Synthesis, Characterization and in vitro Evaluation of 4-(2-Aminoethyl)benzenesulfonamide Schiff Bases against Arboviruses
  作者：Douglas Nakahata、Carlos Corsino、Guilherme de Morais、Gabriele Pereira、Állefe Cruz、Douglas Henrique Pereira、Natasha Cassani、Uriel Enrique Ruiz、Igor Santos、Ana Carolina Jardim、Pedro Corbi

  DOI：10.21577/0103-5053.20240049

  日期：——

  This study presents the synthesis and characterization of five Schiff bases derived from the reaction of 4-(2-aminoethyl)-benzenesulfonamide (compound 1) with corresponding aldehydes, (benzaldehyde, 2-pyridinecarboxaldehyde, 2-quinolinecarboxaldehyde, 8-hydroxy2-quinolinecarboxaldehyde and 4-imidazolecarboxaldehyde, for compounds 2-6, respectively). Characterization was performed by various spectroscopic techniques and supported by density functional theory (DFT) calculations. The crystal structures revealed how the substituent groups influenced the present supramolecular interactions. Compounds 1-4 and 6 showed no cytotoxicity to BHK-21 and VERO E6 cells at the highest concentration of 50 µmol L-1, while compound 5 was cytotoxic at this concentration. Compound 5 was active against the Chikungunya virus at the concentration of 10 µmol L-1, highlighting the effect of the 8-hydroxyquinoline substituent for the antiviral activity. For Zika virus, compound 6 was the only one active at 50 µmol L-1. The results suggest the potential of combining sulfonamides with other chemotypes for further development of antiviral agents, especially in the treatment of arboviral diseases.