tert-butyl (4-oxo-4((4-sulfamoylbenzyl)amino)butyl)carbamate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (4-oxo-4((4-sulfamoylbenzyl)amino)butyl)carbamate
• 英文别名: tert-butyl N-[4-oxo-4-[(4-sulfamoylphenyl)methylamino]butyl]carbamate
• 化学式: C₁₆H₂₅N₃O₅S
• 分子量: 371.458
• InChiKey: MVIWKWWGIPACGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-oxo-4((4-sulfamoylbenzyl)amino)butyl)carbamate 在 盐酸 、 三乙胺 作用下， 以 氯仿 为溶剂， 生成 4-guanidino-N-(4-sulfamoyl-benzyl)-butyramide hydrochloride
  参考文献：
  名称：

  Synthesis of sulfonamides with effective inhibitory action against Porphyromonas gingivalis γ-carbonic anhydrase

  摘要：

  New benzenesulfonamides incorporating GABA or N-α-acetyl-L-lysine scaffolds as well as guanidine functionalities as water solubilizing moieties were obtained, using 4-aminoethyl/methyl-benzenesulfonamide and metanilamide/sulfanilamide as zinc-binding motives. The new compounds were medium potency inhibitors of the widespread cytosolic human carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and more effective inhibitors (KIs low nanomolar range) of the bacterial γ-CA from the oral pathogen Porphyromonas gingivalis. These sulfonamides may be useful tools for understanding the physiological role of bacterial CAs in pathogenesis of some infectious disease.

  DOI：

  10.1016/j.bmcl.2014.06.024
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.0h， 生成 tert-butyl (4-oxo-4((4-sulfamoylbenzyl)amino)butyl)carbamate
  参考文献：
  名称：

  结合有GABA部分的新型脲基取代磺酰胺对人碳酸酐酶同工型I–XIV的抑制作用研究

  摘要：

  γ-BOC-GABA的反应中，通过保护氨基丁酸的γ-氨基部分与制备叔-丁氧基羰基（Boc）保护基，与4-甲基/乙基苯磺酰胺结合，然后在3 M HCl中除去Boc保护基，得到相应的盐酸盐，将其与不同种类的芳基异氰酸酯反应进一步衍生化，得到新的类别含有GABA部分的脲基取代的苯磺酰胺的制备。用这些新化合物对人碳酸酐酶（CA，EC 4.2.1.1）同工型，CA I–XIV的抑制研究表明，它们对hCA III，IV，VA，VI和XIII具有中等至弱的抑制能力，相当有效的抑制能力对hCA I，VI和IX具有抗性，并且对生理相关的hCA II和VII以及两种与肿瘤相关的同工型CA IX和XII具有出色的抑制作用。

  DOI：

  10.1016/j.bmc.2014.10.041

文献信息

• Inhibition studies of new ureido-substituted sulfonamides incorporating a GABA moiety against human carbonic anhydrase isoforms I–XIV
  作者：Mariangela Ceruso、Sabrina Antel、Daniela Vullo、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2014.10.041

  日期：2014.12

  γ-Boc-GABA, prepared by protecting the γ-amino moiety of the amino butyric acid with the tert-butyloxycarbonyl (Boc) protecting group, with 4-methyl/ethyl benzenesulfonamide, followed by removal of the Boc protecting group in 3 M HCl afforded the corresponding hydrochlorides, which were further derivatized by reaction with a varying of aryl isocyanates to give a new classes of ureido substituted benzenesulfonamide

  γ-BOC-GABA的反应中，通过保护氨基丁酸的γ-氨基部分与制备叔-丁氧基羰基（Boc）保护基，与4-甲基/乙基苯磺酰胺结合，然后在3 M HCl中除去Boc保护基，得到相应的盐酸盐，将其与不同种类的芳基异氰酸酯反应进一步衍生化，得到新的类别含有GABA部分的脲基取代的苯磺酰胺的制备。用这些新化合物对人碳酸酐酶（CA，EC 4.2.1.1）同工型，CA I–XIV的抑制研究表明，它们对hCA III，IV，VA，VI和XIII具有中等至弱的抑制能力，相当有效的抑制能力对hCA I，VI和IX具有抗性，并且对生理相关的hCA II和VII以及两种与肿瘤相关的同工型CA IX和XII具有出色的抑制作用。
• Carbonic anhydrase inhibitors. Part 79
  作者：Giovanna Mincione、Luca Menabuoni、Fabrizio Briganti、Francesco Mincione、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/s0928-0987(99)00052-4

  日期：1999.12

  sulfonamides containing amino, imino, hydrazino or hydroxyl groups with N-tert-butoxycarbonyl-gamma-aminobutyric acid (Boc-GABA; Boc=t-butoxycarbonyl) in the presence of carbodiimide derivatives, afforded after removal of the protecting group, a series of water-soluble compounds (as salts of strong acids, such as hydrochloric, trifluoroacetic or trifluoromethane sulfonic). The new derivatives were assayed

  在除去碳二亚胺衍生物之后，提供26种含有氨基，亚氨基，肼基或羟基的芳族/杂环磺酰胺与N-叔丁氧基羰基-γ-氨基丁酸（Boc-GABA； Boc =叔丁氧基羰基）的反应。保护基，是一系列水溶性化合物（作为强酸的盐，例如盐酸，三氟乙酸或三氟甲烷磺酸）。分析了新衍生物作为锌酶碳酸酐酶（CA）的抑制剂，更确切地说，是涉及重要生理过程的三种同工酶CA I，II（胞质形式）和IV（膜结合形式）的抑制剂。一些新化合物有效地抑制了CA II和CA IV（在纳摩尔范围内），这两种同功酶已知在眼睛睫状突中的房水分泌中起关键作用。当已证实有强烈且持久的降低眼内压（IOP）时，将如上所述获得的一些最佳抑制剂以2％水溶液的形式施用于血压正常或青光眼的白化病兔眼中。因此，赋予这些磺酰胺水溶性的氨基酰基尾部，加上其强大的酶抑制性能和平衡的脂质溶解性，似乎是从碳酸酐酶抑制剂类中获得具有有效局部抗青光眼活性的化合物的关键因素。
• Sulfonamides with Potent Inhibitory Action and Selectivity against the α-Carbonic Anhydrase from <i>Vibrio cholerae</i>
  作者：Mariangela Ceruso、Sonia Del Prete、Zeid Alothman、Clemente Capasso、Claudiu T. Supuran

  DOI：10.1021/ml500192a

  日期：2014.7.10

  By using N-alpha-acetyl-L-lysine or GABA scaffolds and the conversion of the terminal amino group to the guanidine one, benzenesulfonamides incorporating water solubilizing moieties were synthesized. The new compounds were medium potency inhibitors of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II, and highly effective, nanomolar inhibitors of the pathogenic bacterial alpha-CA from Vibrio cholerae. These sulfonamides possess good selectivity for inhibiting the bacterial over the mammalian isoforms and may be used as tools to understand the role of bacterial CAs in pathogenesis.
• Synthesis and inhibition potency of novel ureido benzenesulfonamides incorporating GABA as tumor-associated carbonic anhydrase IX and XII inhibitors
  作者：Mariangela Ceruso、Sabrina Antel、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.3109/14756366.2015.1014477

  日期：2016.3.3

  New ureido benzenesulfonamides incorporating a GABA moiety as a linker between the ureido and the sulfonamide functionalities were synthesized and their inhibition potency determined against both the predominant cytosolic (hCA I and II) and the transmembrane tumor-associated (hCA IX and XII) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The majority of these compounds were medium potency inhibitors of the cytosolic isoform hCA I and effective hCA II inhibitors, whereas they showed strong inhibition of the two transmembrane tumor-associated isoforms hCA IX and XII, with K(I)s in nanomolar range. Only one derivative had a good selectivity for inhibition of the tumor-associated hCA IX target isoform over the cytosolic and physiologically dominant off-target hCA I and II, being thus a potential tool to develop new anticancer agents.
• Synthesis of sulfonamides with effective inhibitory action against Porphyromonas gingivalis γ-carbonic anhydrase
  作者：Mariangela Ceruso、Sonia Del Prete、Zeid AlOthman、Sameh M. Osman、Andrea Scozzafava、Clemente Capasso、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2014.06.024

  日期：2014.8

  New benzenesulfonamides incorporating GABA or N-α-acetyl-L-lysine scaffolds as well as guanidine functionalities as water solubilizing moieties were obtained, using 4-aminoethyl/methyl-benzenesulfonamide and metanilamide/sulfanilamide as zinc-binding motives. The new compounds were medium potency inhibitors of the widespread cytosolic human carbonic anhydrase (CA, EC 4.2.1.1) isoforms I and II and more effective inhibitors (KIs low nanomolar range) of the bacterial γ-CA from the oral pathogen Porphyromonas gingivalis. These sulfonamides may be useful tools for understanding the physiological role of bacterial CAs in pathogenesis of some infectious disease.