4-(sulfanilylamino-methyl)-benzenesulfonic acid amide | 345970-47-0

• 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-(sulfanilylamino-methyl)-benzenesulfonic acid amide
• 英文别名: 4-(Sulfanilylamino-methyl)-benzolsulfonsaeure-amid；α-Sulfanilamino-toluolsulfonamid-(4)；Sulfanilsaeure-(4-sulfamoyl-benzylamid)；4-[[(4-Aminophenyl)sulfonylamino]methyl]benzenesulfonamide
• CAS: 345970-47-0
• 化学式: C₁₃H₁₅N₃O₄S₂
• 分子量: 341.412
• InChiKey: HHCXOFYGBAPOJR-UHFFFAOYSA-N

物化性质

• 熔点：
  203 °C
• 沸点：
  621.1±65.0 °C(Predicted)
• 密度：
  1.471±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  149
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(sulfanilylamino-methyl)-benzenesulfonic acid amide 在 氢气 、 三乙胺 作用下， 生成 4-{4-[2-Pyridylmethylamino(thioxo)methylamino]phenylsulfonamidomethyl}-1-benzenesulfonamide
  参考文献：
  名称：

  碳酸酐酶抑制剂：胞嘧啶/肿瘤相关的碳酸酐酶同工酶I，II和IX的合成和抑制，以及掺入硫脲基-磺胺基支架的磺酰胺。

  摘要：

  肿瘤相关的跨膜碳酸酐酶（CA，EC 4.2.1.1）同工酶IX（CA IX）在低氧性肿瘤中过表达，并且似乎参与了肿瘤微环境的酸化，该过程与癌症的进展和不良的预后相关。可以通过用强效的磺酰胺/氨基磺酸CA抑制剂抑制酶来减少酸化作用。已经制备了一系列结合有硫脲基-磺酰苯胺基部分的芳族磺酰胺，并研究了其与人同工酶hCA IX的催化结构域的相互作用。合成中的关键中间体是通过使磺胺，高磺酰胺或4-氨基乙基苯磺酰胺与4-乙酰氨基-苯磺酰氯反应，然后脱乙酰基并与硫光气反应而获得的。使获得的异硫氰酸根合磺酰胺与脂族或芳族伯胺或肼反应，得到相应的硫脲。这些化合物中的某些显示出对同工酶I，II和IX的优异抑制特性，并且几种抑制剂还显示出对CA IX的抑制作用比对普遍存在的同工酶CA II的选择性。基于对在低氧肿瘤中过表达的CA同工酶的抑制作用，此类磺酰胺可能构成开发新型抗肿瘤疗法的有趣候选物。由于CA IX在

  DOI：

  10.1016/j.bmcl.2005.02.087
• 作为产物：
  描述：

  N-苄基乙酰胺 在 吡啶 、 盐酸 、 ammonium hydroxide 、 chlorosulphuric acid 作用下， 生成 4-(sulfanilylamino-methyl)-benzenesulfonic acid amide
  参考文献：
  名称：

  Homosulfanilamides¹

  摘要：

  DOI：

  10.1021/ja01237a012

文献信息

• Carbonic anhydrase inhibitors: Sulfonamides as antitumor agents?
  作者：Claudiu T Supuran、Fabrizio Briganti、Silvia Tilli、W.Richard Chegwidden、Andrea Scozzafava

  DOI：10.1016/s0968-0896(00)00288-1

  日期：2001.3

  inhibitors of human CA I and CA II (hCA I and hCA II) and bovine CA IV (bCA IV). For the most active compounds, inhibition constants ranged from 10(-8) to 10(-9) M (for isozymes II and IV). Three of the derivatives belonging to this new class of CA inhibitors were also tested as inhibitors of tumor cell growth in vitro. These sulfonamides showed potent inhibition of growth against several leukemia, non-small

  新型的锌酶碳酸酐酶的磺酰胺抑制剂（CA，EC 4.2.1.1）是通过在氧化剂（次氯酸钠或次氯酸钠）的存在下，使含氨基，亚氨基或肼基的芳香族或杂环磺酰胺与N，N-二烷基二硫代氨基甲酸酯反应来制备的。碘）。以这种方式合成的N，N-二烷基硫代氨基甲酰基磺酰胺基磺酰胺是人CA I和CA II（hCA I和hCA II）和牛CA IV（bCA IV）的强抑制剂。对于活性最高的化合物，抑制常数范围为10（-8）至10（-9）M（对于同功酶II和IV）。还测试了属于这种新型CA抑制剂的三种衍生物作为体外肿瘤细胞生长的抑制剂。这些磺酰胺类药物对多种白血病，非小细胞肺癌，卵巢癌，黑素瘤，结肠癌，中枢神经系统，肾癌，前列腺和乳腺癌细胞系。具有多个细胞系。观察到GI50值为10-75nM。此处报道的新磺酰胺类药物的抗肿瘤作用机制仍不清楚，但可能涉及抑制在肿瘤细胞膜（CA IX和CA XII）中占主导地位的CA同
• Carbonic anhydrase inhibitors: inhibition of the tumor-associated isozyme IX with fluorine-containing sulfonamides. The first subnanomolar CA IX inhibitor discovered
  作者：Daniela Vullo、Andrea Scozzafava、Silvia Pastorekova、Jaromir Pastorek、Claudiu T Supuran

  DOI：10.1016/j.bmcl.2004.01.095

  日期：2004.5

  properties against different carbonic anhydrase (CA) isozymes, such as CA I, II, and IV, but such compounds have not been tested for their interaction with the transmembrane, tumor-associated isozyme CA IX. Thus, a series of such compounds has been obtained by attaching 2,3,5,6-tetrafluorobenzoyl- and 2,3,5,6-tetrafluorophenylsulfonyl- moieties to aromatic/heterocyclic sulfonamides possessing derivatizable

  多氟化CAI对不同的碳酸酐酶（CA）同功酶（例如CA I，II和IV）显示出非常好的抑制特性，但是尚未测试此类化合物与跨膜，肿瘤相关同功酶CA IX的相互作用。因此，通过将2,3,5,6-四氟苯甲酰基-和2,3,5,6-四氟苯磺酰基-部分连接到具有可衍生氨基部分的芳族/杂环磺酰胺上，获得了一系列这样的化合物。这些化合物中的一些显示出优异的CA IX抑制特性，并且还具有优于CA IX的选择性比，而CA II是对磺酰胺抑制剂具有高亲和力的其他生理相关同工酶。第一亚纳摩尔和而选择性CA IX抑制剂已经发现，为2,3,5，偏甲酰胺的6-四氟苯甲酰基衍生物对hCA IX的抑制常数为0.8 nM，对CA IX的选择性比CA II为26.25。在本文报道的新衍生物中还检测到其他几种低纳摩尔CA IX抑制剂。基于对肿瘤相关的CA同工酶的选择性抑制，所报道的衍生物构成了开发新型抗肿瘤疗法的有价值的候选物。
• Development of Potent Carbonic Anhydrase Inhibitors Incorporating Both Sulfonamide and Sulfamide Groups
  作者：Katia D'Ambrosio、Fatma-Zhora Smaine、Fabrizio Carta、Giuseppina De Simone、Jean-Yves Winum、Claudiu T. Supuran

  DOI：10.1021/jm300818k

  日期：2012.8.9

  A series of compounds incorporating both sulfonamide and sulfamide as zinc-binding groups (ZBGs) are reported as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Crystallographic studies on the complex of hCA II with the lead compound of this series, namely, 4-sulfamido-benzenesulfonamide, revealed the binding of two molecules in the enzyme active site cavity, the first one canonically coordinated to the zinc ion by means of the sulfonamide group and the second one located at the entrance of the cavity. This observation led to the design of elongated molecules incorporating these two ZBGs, separated by a linker of proper length, to allow the simultaneous binding to these different sites. The "long" inhibitors indeed showed around 10 times better enzyme inhibitory properties as compared to the shorter molecules against four physiologically relevant human (h) isoforms, hCA I, II, IX, and XII.
• Jensen; Schmith, Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, 1944, vol. 280, p. 35,38
  作者：Jensen、Schmith

  DOI：——

  日期：——
• Carbonic Anhydrase Inhibitors:  Synthesis and Topical Intraocular Pressure Lowering Effects of Fluorine-Containing Inhibitors Devoid of Enhanced Reactivity
  作者：Xavier de Leval、Monica Ilies、Angela Casini、Jean-Michel Dogné、Andrea Scozzafava、Emanuela Masini、Francesco Mincione、Michele Starnotti、Claudiu T. Supuran

  DOI：10.1021/jm031116j

  日期：2004.5.1

  Polyfluorinated carbonic anhydrase inhibitors (CAIs) show very good inhibitory properties against carbonic anhydrase (CA) and excellent in vivo antiglaucoma properties after topical administration in rabbits. Still, the pentafluorinated compounds reported previously by this group (Scozzafava et al. J. Med. Chem. 2000, 43, 4542-4551) showed high reactivity with thiol groups of cysteine, glutathione, and presumably other proteins containing such moieties, which may lead to severe ocular side effects. Here, we report an approach for obtaining fluorinated CA inhibitors without the undesired enhanced reactivity. Thus, new compounds have been obtained by attaching moieties with reduced reactivity toward aromatic substitution reactions to the molecules of aromatic/heterocyclic sulfonamides possessing derivatizable amino moieties. The employed tails of the 2,3,5,6-tetrafluorobenzoyl, 2,3,5,6-tetrafluophenylsulfonyl, and pentafluorophenylureido types induced excellent CA inhibitory properties in the new reported sulfonamides, mainly against the isozymes involved in aqueous humor secretion, CA II and CA IV, whereas affinity for CA I was lower. Several low-nanomolar CA II inhibitors were detected, which did not react with cysteine or glutathione, in contrast to the corresponding perfluorinated compounds previously reported. These derivatives also showed a potent reduction of the intraocular pressure (IOP) in hypertensive rabbits, amounting to 13-21 mmHg at 1 h postadministration (compared to 5 mmHg obtained with dorzolamide, a clinically used drug), and the decreased IOP was maintained for 4-5 h after the administration. These compounds constitute valuable candidates for obtaining topically acting antiglaucoma CA inhibitors of a new generation, with enhanced efficacy, prolonged duration of action, and reduced side effects.